WorldWideScience

Sample records for genome studies progress

  1. Genome-wide association studies in asthma: progress and pitfalls

    Directory of Open Access Journals (Sweden)

    March ME

    2015-01-01

    Full Text Available Michael E March,1 Patrick MA Sleiman,1,2 Hakon Hakonarson1,2 1Center for Applied Genomics, Children's Hospital of Philadelphia Research Institute, 2Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Abstract: Genetic studies of asthma have revealed that there is considerable heritability to the phenotype. An extensive history of candidate-gene studies has identified a long list of genes associated with immune function that are potentially involved in asthma pathogenesis. However, many of the results of candidate-gene studies have failed to be replicated, leaving in question the true impact of the implicated biological pathways on asthma. With the advent of genome-wide association studies, geneticists are able to examine the association of hundreds of thousands of genetic markers with a phenotype, allowing the hypothesis-free identification of variants associated with disease. Many such studies examining asthma or related phenotypes have been published, and several themes have begun to emerge regarding the biological pathways underpinning asthma. The results of many genome-wide association studies have currently not been replicated, and the large sample sizes required for this experimental strategy invoke difficulties with sample stratification and phenotypic heterogeneity. Recently, large collaborative groups of researchers have formed consortia focused on asthma, with the goals of sharing material and data and standardizing diagnosis and experimental methods. Additionally, research has begun to focus on genetic variants that affect the response to asthma medications and on the biology that generates the heterogeneity in the asthma phenotype. As this work progresses, it will move asthma patients closer to more specific, personalized medicine. Keywords: asthma, genetics, GWAS, pharmacogenetics, biomarkers

  2. Genome-Wide Association of CKD Progression: The Chronic Renal Insufficiency Cohort Study.

    Science.gov (United States)

    Parsa, Afshin; Kanetsky, Peter A; Xiao, Rui; Gupta, Jayanta; Mitra, Nandita; Limou, Sophie; Xie, Dawei; Xu, Huichun; Anderson, Amanda Hyre; Ojo, Akinlolu; Kusek, John W; Lora, Claudia M; Hamm, L Lee; He, Jiang; Sandholm, Niina; Jeff, Janina; Raj, Dominic E; Böger, Carsten A; Bottinger, Erwin; Salimi, Shabnam; Parekh, Rulan S; Adler, Sharon G; Langefeld, Carl D; Bowden, Donald W; Groop, Per-Henrik; Forsblom, Carol; Freedman, Barry I; Lipkowitz, Michael; Fox, Caroline S; Winkler, Cheryl A; Feldman, Harold I

    2017-03-01

    The rate of decline of renal function varies significantly among individuals with CKD. To understand better the contribution of genetics to CKD progression, we performed a genome-wide association study among participants in the Chronic Renal Insufficiency Cohort Study. Our outcome of interest was CKD progression measured as change in eGFR over time among 1331 blacks and 1476 whites with CKD. We stratified all analyses by race and subsequently, diabetes status. Single-nucleotide polymorphisms (SNPs) that surpassed a significance threshold of P<1×10(-6) for association with eGFR slope were selected as candidates for follow-up and secondarily tested for association with proteinuria and time to ESRD. We identified 12 such SNPs among black patients and six such SNPs among white patients. We were able to conduct follow-up analyses of three candidate SNPs in similar (replication) cohorts and eight candidate SNPs in phenotype-related (validation) cohorts. Among blacks without diabetes, rs653747 in LINC00923 replicated in the African American Study of Kidney Disease and Hypertension cohort (discovery P=5.42×10(-7); replication P=0.039; combined P=7.42×10(-9)). This SNP also associated with ESRD (hazard ratio, 2.0 (95% confidence interval, 1.5 to 2.7); P=4.90×10(-6)). Similarly, rs931891 in LINC00923 associated with eGFR decline (P=1.44×10(-4)) in white patients without diabetes. In summary, SNPs in LINC00923, an RNA gene expressed in the kidney, significantly associated with CKD progression in individuals with nondiabetic CKD. However, the lack of equivalent cohorts hampered replication for most discovery loci. Further replication of our findings in comparable study populations is warranted.

  3. Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy

    Science.gov (United States)

    Kouri, Naomi; Ross, Owen A.; Dombroski, Beth; Younkin, Curtis S.; Serie, Daniel J.; Soto-Ortolaza, Alexandra; Baker, Matthew; Finch, Ni Cole A.; Yoon, Hyejin; Kim, Jungsu; Fujioka, Shinsuke; McLean, Catriona A.; Ghetti, Bernardino; Spina, Salvatore; Cantwell, Laura B.; Farlow, Martin R.; Grafman, Jordan; Huey, Edward D.; Ryung Han, Mi; Beecher, Sherry; Geller, Evan T.; Kretzschmar, Hans A.; Roeber, Sigrun; Gearing, Marla; Juncos, Jorge L.; Vonsattel, Jean Paul G.; Van Deerlin, Vivianna M.; Grossman, Murray; Hurtig, Howard I.; Gross, Rachel G.; Arnold, Steven E.; Trojanowski, John Q.; Lee, Virginia M.; Wenning, Gregor K.; White, Charles L.; Höglinger, Günter U.; Müller, Ulrich; Devlin, Bernie; Golbe, Lawrence I.; Crook, Julia; Parisi, Joseph E.; Boeve, Bradley F.; Josephs, Keith A.; Wszolek, Zbigniew K.; Uitti, Ryan J.; Graff-Radford, Neill R.; Litvan, Irene; Younkin, Steven G.; Wang, Li-San; Ertekin-Taner, Nilüfer; Rademakers, Rosa; Hakonarsen, Hakon; Schellenberg, Gerard D.; Dickson, Dennis W.

    2015-01-01

    Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases (n=152) and 3,311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations with meta-analysis were 17q21 at MAPT (P=1.42 × 10−12), 8p12 at lnc-KIF13B-1, a long non-coding RNA (rs643472; P=3.41 × 10−8), and 2p22 at SOS1 (rs963731; P=1.76 × 10−7). Testing for association of CBD with top progressive supranuclear palsy (PSP) GWAS single-nucleotide polymorphisms (SNPs) identified associations at MOBP (3p22; rs1768208; P=2.07 × 10−7) and MAPT H1c (17q21; rs242557; P=7.91 × 10−6). We previously reported SNP/transcript level associations with rs8070723/MAPT, rs242557/MAPT, and rs1768208/MOBP and herein identified association with rs963731/SOS1. We identify new CBD susceptibility loci and show that CBD and PSP share a genetic risk factor other than MAPT at 3p22 MOBP (myelin-associated oligodendrocyte basic protein). PMID:26077951

  4. Inferring tumor progression from genomic heterogeneity.

    Science.gov (United States)

    Navin, Nicholas; Krasnitz, Alexander; Rodgers, Linda; Cook, Kerry; Meth, Jennifer; Kendall, Jude; Riggs, Michael; Eberling, Yvonne; Troge, Jennifer; Grubor, Vladimir; Levy, Dan; Lundin, Pär; Månér, Susanne; Zetterberg, Anders; Hicks, James; Wigler, Michael

    2010-01-01

    Cancer progression in humans is difficult to infer because we do not routinely sample patients at multiple stages of their disease. However, heterogeneous breast tumors provide a unique opportunity to study human tumor progression because they still contain evidence of early and intermediate subpopulations in the form of the phylogenetic relationships. We have developed a method we call Sector-Ploidy-Profiling (SPP) to study the clonal composition of breast tumors. SPP involves macro-dissecting tumors, flow-sorting genomic subpopulations by DNA content, and profiling genomes using comparative genomic hybridization (CGH). Breast carcinomas display two classes of genomic structural variation: (1) monogenomic and (2) polygenomic. Monogenomic tumors appear to contain a single major clonal subpopulation with a highly stable chromosome structure. Polygenomic tumors contain multiple clonal tumor subpopulations, which may occupy the same sectors, or separate anatomic locations. In polygenomic tumors, we show that heterogeneity can be ascribed to a few clonal subpopulations, rather than a series of gradual intermediates. By comparing multiple subpopulations from different anatomic locations, we have inferred pathways of cancer progression and the organization of tumor growth.

  5. The function genomics study

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@ Genomics is a biology term appeared ten years ago, used to describe the researches of genomic mapping, sequencing, and structure analysis, etc. Genomics, the first journal for publishing papers on genomics research was born in 1986. In the past decade, the concept of genomics has been widely accepted by scientists who are engaging in biology research. Meanwhile, the research scope of genomics has been extended continuously, from simple gene mapping and sequencing to function genomics study. To reflect the change, genomics is divided into two parts now, the structure genomics and the function genomics.

  6. The use of whole genome amplification to study chromosomal changes in prostate cancer: insights into genome-wide signature of preneoplasia associated with cancer progression

    Directory of Open Access Journals (Sweden)

    Squire Jeremy A

    2006-03-01

    Full Text Available Abstract Background Prostate cancer (CaP is a disease with multifactorial etiology that includes both genetic and environmental components. The knowledge of the genetic basis of CaP has increased over the past years, mainly in the pathways that underlie tumourigenesis, progression and drug resistance. The vast majority of cases of CaP are adenocarcinomas that likely develop through a pre-malignant lesion and high-grade prostatic intraepithelial neoplasia (HPIN. Histologically, CaP is a heterogeneous disease consisting of multiple, discrete foci of invasive carcinoma and HPIN that are commonly interspersed with benign glands and stroma. This admixture with benign tissue can complicate genomic analyses in CaP. Specifically, when DNA is bulk-extracted the genetic information obtained represents an average for all of the cells within the sample. Results To minimize this problem, we obtained DNA from individual foci of HPIN and CaP by laser capture microdissection (LCM. The small quantities of DNA thus obtained were then amplified by means of multiple-displacement amplification (MDA, for use in genomic DNA array comparative genomic hybridisation (gaCGH. Recurrent chromosome copy number abnormalities (CNAs were observed in both HPIN and CaP. In HPIN, chromosomal imbalances involving chromosome 8 where common, whilst in CaP additional chromosomal changes involving chromosomes 6, 10, 13 and 16 where also frequently observed. Conclusion An overall increase in chromosomal changes was seen in CaP compared to HPIN, suggesting a universal breakdown in chromosomal stability. The accumulation of CNAs, which occurs during this process is non-random and may indicate chromosomal regions important in tumourigenesis. It is therefore likely that the alterations in copy number are part of a programmed cycle of events that promote tumour development, progression and survival. The combination of LCM, MDA and gaCGH is ideally suited for the identification of CNAs from

  7. DOE Joint Genome Institute 2008 Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, David

    2009-03-12

    -based sequencing process that dominated how sequencing was done in the last decade is being replaced by a variety of new processes and sequencing instruments. The JGI, with an increasing number of next-generation sequencers, whose throughput is 100- to 1,000-fold greater than the Sanger capillary-based sequencers, is increasingly focused in new directions on projects of scale and complexity not previously attempted. These new directions for the JGI come, in part, from the 2008 National Research Council report on the goals of the National Plant Genome Initiative as well as the 2007 National Research Council report on the New Science of Metagenomics. Both reports outline a crucial need for systematic large-scale surveys of the plant and microbial components of the biosphere as well as an increasing need for large-scale analysis capabilities to meet the challenge of converting sequence data into knowledge. The JGI is extensively discussed in both reports as vital to progress in these fields of major national interest. JGI's future plan for plants and microbes includes a systematic approach for investigation of these organisms at a scale requiring the special capabilities of the JGI to generate, manage, and analyze the datasets. JGI will generate and provide not only community access to these plant and microbial datasets, but also the tools for analyzing them. These activities will produce essential knowledge that will be needed if we are to be able to respond to the world's energy and environmental challenges. As the JGI Plant and Microbial programs advance, the JGI as a user facility is also evolving. The Institute has been highly successful in bending its technical and analytical skills to help users solve large complex problems of major importance, and that effort will continue unabated. The JGI will increasingly move from a central focus on 'one-off' user projects coming from small user communities to much larger scale projects driven by systematic and problem

  8. DOE Joint Genome Institute 2008 Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, David

    2009-03-12

    -based sequencing process that dominated how sequencing was done in the last decade is being replaced by a variety of new processes and sequencing instruments. The JGI, with an increasing number of next-generation sequencers, whose throughput is 100- to 1,000-fold greater than the Sanger capillary-based sequencers, is increasingly focused in new directions on projects of scale and complexity not previously attempted. These new directions for the JGI come, in part, from the 2008 National Research Council report on the goals of the National Plant Genome Initiative as well as the 2007 National Research Council report on the New Science of Metagenomics. Both reports outline a crucial need for systematic large-scale surveys of the plant and microbial components of the biosphere as well as an increasing need for large-scale analysis capabilities to meet the challenge of converting sequence data into knowledge. The JGI is extensively discussed in both reports as vital to progress in these fields of major national interest. JGI's future plan for plants and microbes includes a systematic approach for investigation of these organisms at a scale requiring the special capabilities of the JGI to generate, manage, and analyze the datasets. JGI will generate and provide not only community access to these plant and microbial datasets, but also the tools for analyzing them. These activities will produce essential knowledge that will be needed if we are to be able to respond to the world's energy and environmental challenges. As the JGI Plant and Microbial programs advance, the JGI as a user facility is also evolving. The Institute has been highly successful in bending its technical and analytical skills to help users solve large complex problems of major importance, and that effort will continue unabated. The JGI will increasingly move from a central focus on 'one-off' user projects coming from small user communities to much larger scale projects driven by systematic and problem

  9. Human Genome Program Report. Part 1, Overview and Progress

    Science.gov (United States)

    1997-11-01

    This report contains Part 1 of a two-part report to reflect research and progress in the U.S. Department of Energy Human Genome Program from 1994 through 1996, with specified updates made just before publication. Part 1 consists of the program overview and report on progress.

  10. Human genome program report. Part 1, overview and progress

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-11-01

    This report contains Part 1 of a two-part report to reflect research and progress in the U.S. Department of Energy Human Genome Program from 1994 through 1996, with specified updates made just before publication. Part 1 consists of the program overview and report on progress.

  11. Genome evolution during progression to breast cancer

    KAUST Repository

    Newburger, D. E.

    2013-04-08

    Cancer evolution involves cycles of genomic damage, epigenetic deregulation, and increased cellular proliferation that eventually culminate in the carcinoma phenotype. Early neoplasias, which are often found concurrently with carcinomas and are histologically distinguishable from normal breast tissue, are less advanced in phenotype than carcinomas and are thought to represent precursor stages. To elucidate their role in cancer evolution we performed comparative whole-genome sequencing of early neoplasias, matched normal tissue, and carcinomas from six patients, for a total of 31 samples. By using somatic mutations as lineage markers we built trees that relate the tissue samples within each patient. On the basis of these lineage trees we inferred the order, timing, and rates of genomic events. In four out of six cases, an early neoplasia and the carcinoma share a mutated common ancestor with recurring aneuploidies, and in all six cases evolution accelerated in the carcinoma lineage. Transition spectra of somatic mutations are stable and consistent across cases, suggesting that accumulation of somatic mutations is a result of increased ancestral cell division rather than specific mutational mechanisms. In contrast to highly advanced tumors that are the focus of much of the current cancer genome sequencing, neither the early neoplasia genomes nor the carcinomas are enriched with potentially functional somatic point mutations. Aneuploidies that occur in common ancestors of neoplastic and tumor cells are the earliest events that affect a large number of genes and may predispose breast tissue to eventual development of invasive carcinoma.

  12. The Cassava Genome: Current Progress, Future Directions.

    Science.gov (United States)

    Prochnik, Simon; Marri, Pradeep Reddy; Desany, Brian; Rabinowicz, Pablo D; Kodira, Chinnappa; Mohiuddin, Mohammed; Rodriguez, Fausto; Fauquet, Claude; Tohme, Joseph; Harkins, Timothy; Rokhsar, Daniel S; Rounsley, Steve

    2012-03-01

    The starchy swollen roots of cassava provide an essential food source for nearly a billion people, as well as possibilities for bioenergy, yet improvements to nutritional content and resistance to threatening diseases are currently impeded. A 454-based whole genome shotgun sequence has been assembled, which covers 69% of the predicted genome size and 96% of protein-coding gene space, with genome finishing underway. The predicted 30,666 genes and 3,485 alternate splice forms are supported by 1.4 M expressed sequence tags (ESTs). Maps based on simple sequence repeat (SSR)-, and EST-derived single nucleotide polymorphisms (SNPs) already exist. Thanks to the genome sequence, a high-density linkage map is currently being developed from a cross between two diverse cassava cultivars: one susceptible to cassava brown streak disease; the other resistant. An efficient genotyping-by-sequencing (GBS) approach is being developed to catalog SNPs both within the mapping population and among diverse African farmer-preferred varieties of cassava. These resources will accelerate marker-assisted breeding programs, allowing improvements in disease-resistance and nutrition, and will help us understand the genetic basis for disease resistance.

  13. Progress in Genome Editing Technology and Its Application in Plants

    OpenAIRE

    Zhang, Kai; Raboanatahiry, Nadia; Zhu, Bin; Li, Maoteng

    2017-01-01

    Genome editing technology (GET) is a versatile approach that has progressed rapidly as a mechanism to alter the genotype and phenotype of organisms. However, conventional genome modification using GET cannot satisfy current demand for high-efficiency and site-directed mutagenesis, retrofitting of artificial nucleases has developed into a new avenue within this field. Based on mechanisms to recognize target genes, newly-developed GETs can generally be subdivided into three cleavage systems, pr...

  14. 2013 Progress Report -- DOE Joint Genome Institute

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-11-01

    In October 2012, we introduced a 10-Year Strategic Vision [http://bit.ly/JGI-Vision] for the Institute. A central focus of this Strategic Vision is to bridge the gap between sequenced genomes and an understanding of biological functions at the organism and ecosystem level. This involves the continued massive-scale generation of sequence data, complemented by orthogonal new capabilities to functionally annotate these large sequence data sets. Our Strategic Vision lays out a path to guide our decisions and ensure that the evolving set of experimental and computational capabilities available to DOE JGI users will continue to enable groundbreaking science.

  15. Genetical Genomics for Evolutionary Studies

    NARCIS (Netherlands)

    Prins, J.C.P.; Smant, G.; Jansen, R.C.

    2012-01-01

    enetical genomics combines acquired high-throughput genomic data with genetic analysis. In this chapter, we discuss the application of genetical genomics for evolutionary studies, where new high-throughput molecular technologies are combined with mapping quantitative trait loci (QTL) on the genome

  16. The genomic dynamics during progression of lung adenocarcinomas.

    Science.gov (United States)

    Yang, Bin; Luo, Longhai; Luo, Wen; Zhou, Yong; Yang, Chao; Xiong, Teng; Li, Xiangchun; Meng, Xuan; Li, Lin; Zhang, Xiaopin; Wang, Zhe; Wang, Zhixin

    2017-08-01

    Intra-tumor heterogeneity is a big barrier to precision medicine. To explore the underlying clonal diversity in lung adenocarcinomas, we selected nine individuals with whole-genome sequencing data from primary and matched metastatic tumors as a cohort for study. Similar global pattern of arm-level copy number changes and large variations of somatic single-nucleotide variant between the primary and metastasis are observed in the majority of cases. Importantly, we found breakage-fusion-bridge (BFB) cycles acting as an important mechanism for underlying cancer gene amplification, such as amplification of CDK4, CDKN3 and FGFR1 in early stage. We also identified recurrent focal amplification of gene CCNY derived from BFB in two metastatic tumors, but not in primary tumor. Clonal analysis of case 236T demonstrated that mutational processes are varying with tumor progression. Collectively, our data provide new insights into genetic diversity and potential therapeutic target in lung adenocarcinoma.

  17. In situ quantification of genomic instability in breast cancer progression

    Energy Technology Data Exchange (ETDEWEB)

    Ortiz de Solorzano, Carlos; Chin, Koei; Gray, Joe W.; Lockett, Stephen J.

    2003-05-15

    Genomic instability is a hallmark of breast and other solid cancers. Presumably caused by critical telomere reduction, GI is responsible for providing the genetic diversity required in the multi-step progression of the disease. We have used multicolor fluorescence in situ hybridization and 3D image analysis to quantify genomic instability cell-by-cell in thick, intact tissue sections of normal breast epithelium, preneoplastic lesions (usual ductal hyperplasia), ductal carcinona is situ or invasive carcinoma of the breast. Our in situ-cell by cell-analysis of genomic instability shows an important increase of genomic instability in the transition from hyperplasia to in situ carcinoma, followed by a reduction of instability in invasive carcinoma. This pattern suggests that the transition from hyperplasia to in situ carcinoma corresponds to telomere crisis and invasive carcinoma is a consequence of telomerase reactivation afertelomere crisis.

  18. Research progress of plant population genomics based on high-throughput sequencing.

    Science.gov (United States)

    Yunsheng, Wang

    2016-08-01

    Population genomics, a new paradigm for population genetics, combine the concepts and techniques of genomics with the theoretical system of population genetics and improve our understanding of microevolution through identification of site-specific effect and genome-wide effects using genome-wide polymorphic sites genotypeing. With the appearance and improvement of the next generation high-throughput sequencing technology, the numbers of plant species with complete genome sequences increased rapidly and large scale resequencing has also been carried out in recent years. Parallel sequencing has also been done in some plant species without complete genome sequences. These studies have greatly promoted the development of population genomics and deepened our understanding of the genetic diversity, level of linking disequilibium, selection effect, demographical history and molecular mechanism of complex traits of relevant plant population at a genomic level. In this review, I briely introduced the concept and research methods of population genomics and summarized the research progress of plant population genomics based on high-throughput sequencing. I also discussed the prospect as well as existing problems of plant population genomics in order to provide references for related studies.

  19. Genomic-Glycosylation Aberrations in Tumor Initiation, Progression and Management

    Directory of Open Access Journals (Sweden)

    Carman K.M. Ip

    2016-12-01

    Full Text Available Post-translation modifications of proteins alter their functional activity and thus are key contributors of tumor initiation and progression. Glycosylation, one of the most common post-translational modifications of proteins, has been associated with tumorigenesis for decades. However, due to complexity in analysis of the functional effects of glycosylation, definitive information on the role of altered glycosylation in cancer is lacking. Importantly, imputing changes in glycosylation in proteins from analysis of DNA mutations has not been attempted globally. It is thus critical to elucidate the role of glycosylation in tumor pathophysiology as well as potential roles of altered glycosylation as cancer biomarkers and therapeutic targets. In this review, we summarize the evidence that glycosylation regulates functions of a set of frequently mutated oncogenes and tumor suppressors. Moreover, we explore the potential that protein sequence changes engendered by genomic mutations broadly alter glycosylation and thus promote tumor initiation and progression.

  20. Genomic aberrations of myeloproliferative and myelodysplastic/myeloproliferative neoplasms in chronic phase and during disease progression.

    Science.gov (United States)

    Hahm, C; Huh, H J; Mun, Y C; Seong, C M; Chung, W S; Huh, J

    2015-04-01

    Myeloproliferative neoplasms (MPN) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) may transform into secondary myelofibrosis (MF) or evolve into acute myeloid leukemia (AML). The genetic mechanisms underlying disease progression in MPN and MDS/MPN patients remain unclear. The purpose of this study was to investigate sequential genomic aberrations identified by single nucleotide polymorphism array (SNP-A)-based karyotyping that can detect cryptic aberrations or copy neutral loss of heterozygosity (CN-LOH) in the chronic phase and during disease progression of MPN and MDS/MPN patients. The study group included 13 MPN and four MDS/MPN patients (seven polycythemia vera (PV); four essential thrombocythemia (ET); two MPN-unclassifiable (MPN-U); one chronic myelomonocytic leukemia (CMML); one atypical chronic myeloid leukemia, BCR-ABL1 negative (aCML); and two MDS/MPN-unclassifiable (MDS/MPN-U)). Among them, five patients (two PV, two MPN-U, and one MDS/MPN-U) progressed to MF and three patients (one CMML, one aCML, and one MDS/MPN-U) transformed to AML. The median follow-up period was 70 months (range, 7-152). Whole-genome SNP-A (SNP 6.0; Affymetrix, Santa Clara, CA, USA)-based karyotyping and JAK2 mutation analysis were performed according to the manufacturer's instructions. SNP-A showed 19 kinds of genomic aberrations, including seven gains, eight deletions, and four CN-LOH. CN-LOH of 9p involving JAK2 was the most common aberration, followed by 5q deletion and 9p gain. The incidence of genomic changes identified by SNP was not different in patients with disease progression (75%), compared with those without disease progression (56%) (P = 0.4). However, when excluding 9p CN-LOH, the incidence of genomic changes was significantly higher in patients with disease progression than in patients without disease progression (63% and 0%, respectively, P = 0.01). Among eight patients with disease progression, two patients (two MPN-U) showed abnormal SNP-A results

  1. Progress in Genome Editing Technology and Its Application in Plants

    Science.gov (United States)

    Zhang, Kai; Raboanatahiry, Nadia; Zhu, Bin; Li, Maoteng

    2017-01-01

    Genome editing technology (GET) is a versatile approach that has progressed rapidly as a mechanism to alter the genotype and phenotype of organisms. However, conventional genome modification using GET cannot satisfy current demand for high-efficiency and site-directed mutagenesis, retrofitting of artificial nucleases has developed into a new avenue within this field. Based on mechanisms to recognize target genes, newly-developed GETs can generally be subdivided into three cleavage systems, protein-dependent DNA cleavage systems (i.e., zinc-finger nucleases, ZFN, and transcription activator-like effector nucleases, TALEN), RNA-dependent DNA cleavage systems (i.e., clustered regularly interspaced short palindromic repeats-CRISPR associated proteins, CRISPR-Cas9, CRISPR-Cpf1, and CRISPR-C2c1), and RNA-dependent RNA cleavage systems (i.e., RNA interference, RNAi, and CRISPR-C2c2). All these techniques can lead to double-stranded (DSB) or single-stranded breaks (SSB), and result in either random mutations via non-homologous end-joining (NHEJ) or targeted mutation via homologous recombination (HR). Thus, site-directed mutagenesis can be induced via targeted gene knock-out, knock-in, or replacement to modify specific characteristics including morphology-modification, resistance-enhancement, and physiological mechanism-improvement along with plant growth and development. In this paper, an non-comprehensive review on the development of different GETs as applied to plants is presented. PMID:28261237

  2. Progress in Genome Editing Technology and Its Application in Plants.

    Science.gov (United States)

    Zhang, Kai; Raboanatahiry, Nadia; Zhu, Bin; Li, Maoteng

    2017-01-01

    Genome editing technology (GET) is a versatile approach that has progressed rapidly as a mechanism to alter the genotype and phenotype of organisms. However, conventional genome modification using GET cannot satisfy current demand for high-efficiency and site-directed mutagenesis, retrofitting of artificial nucleases has developed into a new avenue within this field. Based on mechanisms to recognize target genes, newly-developed GETs can generally be subdivided into three cleavage systems, protein-dependent DNA cleavage systems (i.e., zinc-finger nucleases, ZFN, and transcription activator-like effector nucleases, TALEN), RNA-dependent DNA cleavage systems (i.e., clustered regularly interspaced short palindromic repeats-CRISPR associated proteins, CRISPR-Cas9, CRISPR-Cpf1, and CRISPR-C2c1), and RNA-dependent RNA cleavage systems (i.e., RNA interference, RNAi, and CRISPR-C2c2). All these techniques can lead to double-stranded (DSB) or single-stranded breaks (SSB), and result in either random mutations via non-homologous end-joining (NHEJ) or targeted mutation via homologous recombination (HR). Thus, site-directed mutagenesis can be induced via targeted gene knock-out, knock-in, or replacement to modify specific characteristics including morphology-modification, resistance-enhancement, and physiological mechanism-improvement along with plant growth and development. In this paper, an non-comprehensive review on the development of different GETs as applied to plants is presented.

  3. Convergence of advances in genomics, team science, and repositories as drivers of progress in psychiatric genomics.

    Science.gov (United States)

    Lehner, Thomas; Senthil, Geetha; Addington, Anjené M

    2015-01-01

    After many years of unfilled promise, psychiatric genetics has seen an unprecedented number of successes in recent years. We hypothesize that the field has reached an inflection point through a confluence of four key developments: advances in genomics; the orientation of the scientific community around large collaborative team science projects; the development of sample and data repositories; and a policy framework for sharing and accessing these resources. We discuss these domains and their effect on scientific progress and provide a perspective on why we think this is only the beginning of a new era in scientific discovery.

  4. Multi-platform genome-wide analysis of melanoma progression to brain metastasis

    Directory of Open Access Journals (Sweden)

    Diego M. Marzese

    2014-12-01

    Full Text Available Melanoma has a high tendency to metastasize to brain tissue. The understanding about the molecular alterations of early-stage melanoma progression to brain metastasis (MBM is very limited. Identifying MBM-specific genomic and epigenomic alterations is a key initial step in understanding its aggressive nature and identifying specific novel druggable targets. Here, we describe a multi-platform dataset generated with different stages of melanoma progression to MBM. This data includes genome-wide DNA methylation (Illumina HM450K BeadChip, gene expression (Affymetrix HuEx 1.0 ST array, single nucleotide polymorphisms (SNPs and copy number variation (CNV; Affymetrix SNP 6.0 array analyses of melanocyte cells (MNCs, primary melanoma tumors (PRMs, lymph node metastases (LNMs and MBMs. The analysis of this data has been reported in our recently published study (Marzese et al., 2014.

  5. 78 FR 47674 - Genome in a Bottle Consortium-Progress and Planning Workshop

    Science.gov (United States)

    2013-08-06

    ... National Institute of Standards and Technology Genome in a Bottle Consortium--Progress and Planning... workshop. SUMMARY: NIST announces the Genome in a Bottle Consortium meeting to be held on Thursday and Friday, August 15 and 16, 2013. The Genome in a Bottle Consortium is developing the reference...

  6. Progress in the detection of human genome structural variations

    Institute of Scientific and Technical Information of China (English)

    WU XueMei; XIAO HuaSheng

    2009-01-01

    The emerging of high.throughput and high-resolution genomic technologies led to the detection of submicroscopic variants ranging from 1 kb to 3 Mb in the human genome. These variants include copy number variations (CNVs), inversions, insertions, deletions and other complex rearrangements of DNA sequences. This paper briefly reviews the commonly used technologies to discover both genomic structural variants and their potential influences. Particularly, we highlight the array-based, PCR-based and sequencing-based assays, including array-based comparative genomic hybridization (aCGH),representational oligonucleotide microarray analysis (ROMA), multiplex amplifiable probe hybridization (MAPH), multiplex ligation-dependent probe amplification (MLPA), paired-end mapping (PEM), and next-generation DNA sequencing technologies. Furthermore, we discuss the limitations and challenges of current assays and give advices on how to make the database of genomic variations more reliable.

  7. Progress in the detection of human genome structural variations

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The emerging of high-throughput and high-resolution genomic technologies led to the detection of submicroscopic variants ranging from 1 kb to 3 Mb in the human genome.These variants include copy number variations(CNVs),inversions,insertions,deletions and other complex rearrangements of DNA sequences.This paper briefly reviews the commonly used technologies to discover both genomic structural variants and their potential influences.Particularly,we highlight the array-based,PCR-based and sequencing-based assays,including array-based comparative genomic hybridization(aCGH),representational oligonucleotide microarray analysis(ROMA),multiplex amplifiable probe hybridization(MAPH),multiplex ligation-dependent probe amplification(MLPA),paired-end mapping(PEM),and next-generation DNA sequencing technologies.Furthermore,we discuss the limitations and challenges of current assays and give advices on how to make the database of genomic variations more reliable.

  8. Progress in TILLING as a tool for functional genomics and improvement of crops

    Institute of Scientific and Technical Information of China (English)

    Liang Chen; Liugen Hao; Martin A.J.Parry; Andrew L. Phillips; Yin-Gang Hu

    2014-01-01

    Food security is a global concern and substantial yield increases in crops are required to feed the growing world population. Mutagenesis is an important tool in crop improve-ment and is free of the regulatory restrictions imposed on genetical y modified organisms. Targeting Induced Local Lesions in Genomes (TILLING), which combines traditional chemical mutagenesis with high-throughput genome-wide screening for point mutations in desired genes, offers a powerful way to create novel mutant al eles for both functional genomics and improvement of crops. TILLING is general y applicable to genomes whether smal or large, diploid or even al ohexaploid, and shows great potential to address the major chal enge of linking sequence information to the function of genes and to modulate key traits for plant breeding. TILLING has been successful y applied in many crop species and recent progress in TILLING is summarized below, especial y on the developments in mutation detection technology, application of TILLING in gene functional studies and crop breeding. The potential of TILLING/EcoTILLING for functional genetics and crop improvement is also discussed. Furthermore, a smal-scale forward strategy including backcross and selfing was con-ducted to release the potential mutant phenotypes masked in M2 (or M3) plants.

  9. Genome-wide association and linkage analyses localize a progressive retinal atrophy locus in Persian cats.

    Science.gov (United States)

    Alhaddad, Hasan; Gandolfi, Barbara; Grahn, Robert A; Rah, Hyung-Chul; Peterson, Carlyn B; Maggs, David J; Good, Kathryn L; Pedersen, Niels C; Lyons, Leslie A

    2014-08-01

    Hereditary eye diseases of animals serve as excellent models of human ocular disorders and assist in the development of gene and drug therapies for inherited forms of blindness. Several primary hereditary eye conditions affecting various ocular tissues and having different rates of progression have been documented in domestic cats. Gene therapy for canine retinopathies has been successful, thus the cat could be a gene therapy candidate for other forms of retinal degenerations. The current study investigates a hereditary, autosomal recessive, retinal degeneration specific to Persian cats. A multi-generational pedigree segregating for this progressive retinal atrophy was genotyped using a 63 K SNP array and analyzed via genome-wide linkage and association methods. A multi-point parametric linkage analysis localized the blindness phenotype to a ~1.75 Mb region with significant LOD scores (Z ≈ 14, θ = 0.00) on cat chromosome E1. Genome-wide TDT, sib-TDT, and case-control analyses also consistently supported significant association within the same region on chromosome E1, which is homologous to human chromosome 17. Using haplotype analysis, a ~1.3 Mb region was identified as highly associated for progressive retinal atrophy in Persian cats. Several candidate genes within the region are reasonable candidates as a potential causative gene and should be considered for molecular analyses.

  10. Research progress of genome editing and derivative technologies in plants.

    Science.gov (United States)

    Qiwei, Shan; Caixia, Gao

    2015-10-01

    Genome editing technologies using engineered nucleases have been widely used in many model organisms. Genome editing with sequence-specific nuclease (SSN) creates DNA double-strand breaks (DSBs) in the genomic target sites that are primarily repaired by the non-homologous end joining (NHEJ) or homologous recombination (HR) pathways, which can be employed to achieve targeted genome modifications such as gene mutations, insertions, replacements or chromosome rearrangements. There are three major SSNs─zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9) system. In contrast to ZFN and TALEN, which require substantial protein engineering to each DNA target, the CRISPR/Cas9 system requires only a change in the guide RNA. For this reason, the CRISPR/Cas9 system is a simple, inexpensive and versatile tool for genome engineering. Furthermore, a modified version of the CRISPR/Cas9 system has been developed to recruit heterologous domains that can regulate endogenous gene expression, such as activation, depression and epigenetic regulation. In this review, we summarize the development and applications of genome editing technologies for basic research and biotechnology, as well as highlight challenges and future directions, with particular emphasis on plants.

  11. Genomics technologies to study structural variations in the grapevine genome

    Directory of Open Access Journals (Sweden)

    Cardone Maria Francesca

    2016-01-01

    Full Text Available Grapevine is one of the most important crop plants in the world. Recently there was great expansion of genomics resources about grapevine genome, thus providing increasing efforts for molecular breeding. Current cultivars display a great level of inter-specific differentiation that needs to be investigated to reach a comprehensive understanding of the genetic basis of phenotypic differences, and to find responsible genes selected by cross breeding programs. While there have been significant advances in resolving the pattern and nature of single nucleotide polymorphisms (SNPs on plant genomes, few data are available on copy number variation (CNV. Furthermore association between structural variations and phenotypes has been described in only a few cases. We combined high throughput biotechnologies and bioinformatics tools, to reveal the first inter-varietal atlas of structural variation (SV for the grapevine genome. We sequenced and compared four table grape cultivars with the Pinot noir inbred line PN40024 genome as the reference. We detected roughly 8% of the grapevine genome affected by genomic variations. Taken into account phenotypic differences existing among the studied varieties we performed comparison of SVs among them and the reference and next we performed an in-depth analysis of gene content of polymorphic regions. This allowed us to identify genes showing differences in copy number as putative functional candidates for important traits in grapevine cultivation.

  12. From genome to proteome: great progress in the domesticated silkworm (Bombyx mori L.)

    Institute of Scientific and Technical Information of China (English)

    Zhonghua Zhou; Huijuan Yang; Boxiong Zhong

    2008-01-01

    As the only truly domesticated insect,the silkworm not only has great economic value,but it also has value as a model for genetics and molecular biology research.Genomics and proteomics have recently shown vast potential to be essential tools in domesticated silkworm research,especially after the completion of the Bombyx mori genome sequence.This paper reviews the progress of the domesticated silkworm genome,particularly focusing on its genetic map,physical map and functional genome.This review also presents proteomics,the proteomic technique and its application in silkworm research.

  13. DNA sequencing leads to genomics progress in China

    Institute of Scientific and Technical Information of China (English)

    WU JiaYan; XIAO JingFa; ZHANG RuoSi; YU Jun

    2011-01-01

    1 Science in the large-scale sequencing era Ten years ago,the first draft sequence assembly of the human genome was completed [1],bringing biomedical research one-step closer toward the goal of revolutionizing diagnosis,prevention,and treatment of human diseases.Recently,journalists from the journal Nature surveyed more than 1000 life scientists regarding this laudable aim [2],obtaining substantially negative responses [3].However,almost all of those surveyed had been influenced,in one way or another,by the availability of the human genome sequence,and they also agreed with the notion that the "sequence is the start." The complexity of genome biology and almost every aspect of human biology is far greater than previously thought [4].

  14. Research progress in genomics of environmental and industrial microorganisms

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Microbes contribute to geochemical cycles in the ecosystem.They also play important roles in biodegradation and bioremediation of contaminated environments,and have great potential in energy conversion and regeneration.Up to date,at least 150 genomes of non-pathogenic microbes have been sequenced,of which,the majority are bacteria from various environments or of industrial uses.The emerging field ’metagenomics’ in combination with the high-throughput sequencing technology offers opportunities to discover new functions of microbes in the environment on a large scale,and has become the ’hot spot’ in the field of environmental microbiology.Seven genomes of bacteria from various extreme environments,including high temperature,high and low pressure,and extreme acidic regions,have been sequenced by researchers in China,leading to the discovery of metabolic pathways,genetic functions and new enzymes,which are related to the niches those bacteria occupy.These results were published in Nature,PNAS,Genome Research and other top international journals.In the meantime,several groups in China have started ’metagenomics’ programs.The outcomes of these researches are expected to generate a considerable number of novel findings,taking Chinese researchers to the frontier of genomics for environmental and industrial microorganisms.

  15. Research progress in genomics of environmental and industrial microorganisms

    Institute of Scientific and Technical Information of China (English)

    WANG Lei; LIU Bin; ZHOU ZheMin

    2009-01-01

    Microbes contribute to geochemical cycles in the ecosystem. They also play important roles in bio-degradation and bioremediation of contaminated environments, and have great potential in energy conversion and regeneration. Up to date, at least 150 genomes of non-pathogenic microbes have been sequenced, of which, the majority are bacteria from various environments or of industrial uses. The emerging field 'metagenomics' in combination with the high-throughput sequencing technology offers opportunities to discover new functions of microbes in the environment on a large scale, and has be-come the 'hot spot' in the field of environmental microbiology. Seven genomes of bacteria from various extreme environments, including high temperature, high and low pressure, and extreme acidic regions, have been sequenced by researchers in China, leading to the discovery of metabolic pathways, genetic functions and new enzymes, which are related to the niches those bacteria occupy. These results were published in Nature, PNAS, Genome Research and other top international journals. In the meantime, several groups in China have started 'metagenomics' programs. The outcomes of these researches are expected to generate a considerable number of novel findings, taking Chinese researchers to the fron-tier of genomics for environmental and industrial microorganisms.

  16. Progress on HELIAS systems studies

    Energy Technology Data Exchange (ETDEWEB)

    Warmer, Felix; Beidler, Craig D.; Dinklage, Andreas; Feng, Yuehe; Geiger, Joachim; Schauer, Felix; Turkin, Yuriy; Wolf, Robert; Xanthopoulos, Pavlos [Max-Planck-Institut fuer Plasmaphysik, D-17491 Greifswald (Germany); Kemp, Richard; Knight, Peter; Ward, David [Culham Centre for Fusion Energy, Abingdon, Oxfordshire, OX14 3DB (United Kingdom)

    2015-05-01

    In order to study and design next-step fusion devices such as DEMO, comprehensive systems codes are commonly employed. For the HELIAS-line, stellarator-specific models have been developed, implemented, and verified within the systems code PROCESS. This systems code ansatz is complemented by self-consistent modeling of plasma scenarios employing a predictive 1-D neoclassical transport code which has been augmented with a model for the edge anomalous transport based on 3-D ITG turbulence simulations. This approach is investigated to ultimately allow one to conduct stellarator system studies, develop design points of HELIAS burning plasma devices, and to facilitate a direct comparison between tokamak and stellarator DEMO and power plant designs. The work reports on the progress towards these goals.

  17. Electric fish genomics: Progress, prospects, and new tools for neuroethology.

    Science.gov (United States)

    Pitchers, William R; Constantinou, Savvas J; Losilla, Mauricio; Gallant, Jason R

    2016-10-01

    Electric fish have served as a model system in biology since the 18th century, providing deep insight into the nature of bioelectrogenesis, the molecular structure of the synapse, and brain circuitry underlying complex behavior. Neuroethologists have collected extensive phenotypic data that span biological levels of analysis from molecules to ecosystems. This phenotypic data, together with genomic resources obtained over the past decades, have motivated new and exciting hypotheses that position the weakly electric fish model to address fundamental 21(st) century biological questions. This review article considers the molecular data collected for weakly electric fish over the past three decades, and the insights that data of this nature has motivated. For readers relatively new to molecular genetics techniques, we also provide a table of terminology aimed at clarifying the numerous acronyms and techniques that accompany this field. Next, we pose a research agenda for expanding genomic resources for electric fish research over the next 10years. We conclude by considering some of the exciting research prospects for neuroethology that electric fish genomics may offer over the coming decades, if the electric fish community is successful in these endeavors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Comparative genomics of Bordetella pertussis reveals progressive gene loss in Finnish strains.

    Directory of Open Access Journals (Sweden)

    Eriikka Heikkinen

    Full Text Available BACKGROUND: Bordetella pertussis is a gram-negative bacterium that infects the human respiratory tract and causes pertussis or whooping cough. The disease has resurged in many countries including Finland where the whole-cell pertussis vaccine has been used for more than 50 years. Antigenic divergence has been observed between vaccine strains and clinical isolates in Finland. To better understand genome evolution in B. pertussis circulating in the immunized population, we developed an oligonucleotide-based microarray for comparative genomic analysis of Finnish strains isolated during the period of 50 years. METHODOLOGY/PRINCIPAL FINDINGS: The microarray consisted of 3,582 oligonucleotides (70-mer and covered 94% of 3,816 ORFs of Tohama I, the strain of which the genome has been sequenced. Twenty isolates from 1953 to 2004 were studied together with two Finnish vaccine strains and two international reference strains. The isolates were selected according to their characteristics, e.g. the year and place of isolation and pulsed-field gel electrophoresis profiles. Genomic DNA of the tested strains, along with reference DNA of Tohama I strain, was labelled and hybridized. The absence of genes as established with microarrays, was confirmed by PCR. Compared with the Tohama I strain, Finnish isolates lost 7 (8.6 kb to 49 (55.3 kb genes, clustered in one to four distinct loci. The number of lost genes increased with time, and one third of lost genes had functions related to inorganic ion transport and metabolism, or energy production and conversion. All four loci of lost genes were flanked by the insertion sequence element IS481. CONCLUSION/SIGNIFICANCE: Our results showed that the progressive gene loss occurred in Finnish B. pertussis strains isolated during a period of 50 years and confirmed that B. pertussis is dynamic and is continuously evolving, suggesting that the bacterium may use gene loss as one strategy to adapt to highly immunized populations.

  19. ETS-Associated Genomic Alterations including ETS2 Loss Markedly Affect Prostate Cancer Progression

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-13-1-0385 TITLE: ETS -Associated Genomic Alterations including ETS2 Loss Markedly Affect Prostate Cancer Progression...29 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-13-1-0385 ETS -Associated Genomic Alterations including ETS2 Loss Markedly Affect...upregulation of ERG, a transcription factor with oncogenic roles in other cancers such as leukemias and sarcomas (Tomlins, Rhodes et al. 2005; Turner

  20. Ancient population genomics and the study of evolution.

    Science.gov (United States)

    Parks, M; Subramanian, S; Baroni, C; Salvatore, M C; Zhang, G; Millar, C D; Lambert, D M

    2015-01-19

    Recently, the study of ancient DNA (aDNA) has been greatly enhanced by the development of second-generation DNA sequencing technologies and targeted enrichment strategies. These developments have allowed the recovery of several complete ancient genomes, a result that would have been considered virtually impossible only a decade ago. Prior to these developments, aDNA research was largely focused on the recovery of short DNA sequences and their use in the study of phylogenetic relationships, molecular rates, species identification and population structure. However, it is now possible to sequence a large number of modern and ancient complete genomes from a single species and thereby study the genomic patterns of evolutionary change over time. Such a study would herald the beginnings of ancient population genomics and its use in the study of evolution. Species that are amenable to such large-scale studies warrant increased research effort. We report here progress on a population genomic study of the Adélie penguin (Pygoscelis adeliae). This species is ideally suited to ancient population genomic research because both modern and ancient samples are abundant in the permafrost conditions of Antarctica. This species will enable us to directly address many of the fundamental questions in ecology and evolution. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  1. Molecular genetics and genomics progress in urothelial bladder cancer.

    Science.gov (United States)

    Netto, George J

    2013-11-01

    The clinical management of solid tumor patients has recently undergone a paradigm shift as the result of the accelerated advances in cancer genetics and genomics. Molecular diagnostics is now an integral part of routine clinical management in lung, colon, and breast cancer patients. In a disappointing contrast, molecular biomarkers remain largely excluded from current management algorithms of urologic malignancies. The need for new treatment alternatives and validated prognostic molecular biomarkers that can help clinicians identify patients in need of early aggressive management is pressing. Identifying robust predictive biomarkers that can stratify response to newly introduced targeted therapeutics is another crucially needed development. The following is a brief discussion of some promising candidate biomarkers that may soon become a part of clinical management of bladder cancers.

  2. Genome-wide association study of swine farrowing traits. Part I: genetic and genomic parameter estimates.

    Science.gov (United States)

    Schneider, J F; Rempel, L A; Rohrer, G A

    2012-10-01

    The primary objective of this study was to determine genetic and genomic parameters among swine (Sus scrofa) farrowing traits. Genetic parameters were obtained using MTDFREML. Genomic parameters were obtained using GENSEL. Genetic and residual variances obtained from MTDFREML were used as priors for the Bayes C analysis of GENSEL. Farrowing traits included total number born (TNB), number born alive (NBA), number born dead (NBD), number stillborn (NSB), number of mummies (MUM), litter birth weight (LBW), and average piglet birth weight (ABW). Statistically significant heritabilities included TNB (0.09, P = 0.048), NBA (0.09, P = 0.041), LBW (0.20, P = 0.002), and ABW (0.26, P ABW (0.63, P ABW (0.31). Limited information is available in the literature about genomic parameters. Only the GP estimate for NSB is significantly lower than what has been published. The GP estimate for ABW is greater than the estimate for heritability found in this study. Other traits with significant heritability had GP estimates half the value of heritability. This research indicates that significant genetic markers will be found for TNB, NBA, LBW, and ABW that will have either immediate use in industry or provide a roadmap to further research with fine mapping or sequencing of areas of significance. Furthermore, these results indicate that genomic selection implemented at an early age would have similar annual progress as traditional selection, and could be incorporated along with traditional selection procedures to improve genetic progress of litter traits.

  3. Digging Up the Human Genome: Current Progress in Deciphering Adverse Drug Reactions

    Directory of Open Access Journals (Sweden)

    Shih-Chi Su

    2014-01-01

    Full Text Available Adverse drug reactions (ADRs are a major clinical problem. In addition to their clinical impact on human health, there is an enormous cost associated with ADRs in health care and pharmaceutical industry. Increasing studies revealed that genetic variants can determine the susceptibility of individuals to ADRs. The development of modern genomic technologies has led to a tremendous advancement of improving the drug safety and efficacy and minimizing the ADRs. This review will discuss the pharmacogenomic techniques used to unveil the determinants of ADRs and summarize the current progresses concerning the identification of biomarkers for ADRs, with a focus on genetic variants for genes encoding drug-metabolizing enzymes, drug-transporter proteins, and human leukocyte antigen (HLA. The knowledge gained from these cutting-edge findings will form the basis for better prediction and management for ADRs, ultimately making the medicine personalized.

  4. Genome-wide gene expression profiling of testicular carcinoma in situ progression into overt tumours

    DEFF Research Database (Denmark)

    Almstrup, K; Hoei-Hansen, C E; Nielsen, J E

    2005-01-01

    into CIS occurs early during foetal life. Progression into an overt tumour, however, typically first happens after puberty, where CIS cells transform into either a seminoma (SEM) or a nonseminoma (N-SEM). Here, we have compared the genome-wide gene expression of CIS cells to that of testicular SEM...

  5. [Research progress in developing reporter systems for the enrichment of positive cells with targeted genome modification].

    Science.gov (United States)

    Bai, Yichun; Xu, Kun; Wei, Zehui; Ma, Zheng; Zhang, Zhiying

    2016-01-01

    Targeted genome editing technology plays an important role in studies of gene function, gene therapy and transgenic breeding. Moreover, the efficiency of targeted genome editing is increased dramatically with the application of recently developed artificial nucleases such as ZFNs, TALENs and CRISPR/Cas9. However, obtaining positive cells with targeted genome modification is restricted to some extent by nucleases expression plasmid transfection efficiency, nucleases expression and activity, and repair efficiency after genome editing. Thus, the enrichment and screening of positive cells with targeted genome modification remains a problem that need to be solved. Surrogate reporter systems could be used to reflect the efficiency of nucleases indirectly and enrich genetically modified positive cells effectively, which may increase the efficiency of the enrichment and screening of positive cells with targeted genome modification. In this review, we mainly summarized principles and applications of reporter systems based on NHEJ and SSA repair mechanisms, which may provide references for related studies in future.

  6. Nuclear spectroscopic studies. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Bingham, C.R.; Riedinger, L.L.; Sorensen, S.P.

    1996-01-16

    This report describes progress in the experimental nuclear physics program of the University of Tennessee, Knoxville. It presents findings related to properties of high-spin states, low-energy levels of nuclei far from stability, and high-energy heavy-ion physics, as well as a brief description of the Joint Institute of Heavy Ion Research (a collaboration between the University of Tennessee, Vanderbilt University, and Oak Ridge National Laboratory) and its activities (particularly those of the last few years), and a list of publications. 89 refs., 18 figs., 5 tabs.

  7. Genome-Wide Search for Host Association Factors during Ovine Progressive Pneumonia Virus Infection.

    Directory of Open Access Journals (Sweden)

    Jesse Thompson

    Full Text Available Ovine progressive pneumonia virus (OPPV is an important virus that causes serious diseases in sheep and goats with a prevalence of 36% in the USA. Although OPPV was discovered more than half of a century ago, little is known about the infection and pathogenesis of this virus. In this report, we used RNA-seq technology to conduct a genome-wide probe for cellular factors that are associated with OPPV infection. A total of approximately 22,000 goat host genes were detected of which 657 were found to have been significantly up-regulated and 889 down-regulated at 12 hours post-infection. In addition to previously known restriction factors from other viral infections, a number of factors which may be specific for OPPV infection were uncovered. The data from this RNA-seq study will be helpful in our understanding of OPPV infection, and also for further study in the prevention and intervention of this viral disease.

  8. Phosphorylation of EB2 by Aurora B and CDK1 ensures mitotic progression and genome stability.

    Science.gov (United States)

    Iimori, Makoto; Watanabe, Sugiko; Kiyonari, Shinichi; Matsuoka, Kazuaki; Sakasai, Ryo; Saeki, Hiroshi; Oki, Eiji; Kitao, Hiroyuki; Maehara, Yoshihiko

    2016-03-31

    Temporal regulation of microtubule dynamics is essential for proper progression of mitosis and control of microtubule plus-end tracking proteins by phosphorylation is an essential component of this regulation. Here we show that Aurora B and CDK1 phosphorylate microtubule end-binding protein 2 (EB2) at multiple sites within the amino terminus and a cluster of serine/threonine residues in the linker connecting the calponin homology and end-binding homology domains. EB2 phosphorylation, which is strictly associated with mitotic entry and progression, reduces the binding affinity of EB2 for microtubules. Expression of non-phosphorylatable EB2 induces stable kinetochore microtubule dynamics and delays formation of bipolar metaphase plates in a microtubule binding-dependent manner, and leads to aneuploidy even in unperturbed mitosis. We propose that Aurora B and CDK1 temporally regulate the binding affinity of EB2 for microtubules, thereby ensuring kinetochore microtubule dynamics, proper mitotic progression and genome stability.

  9. Progress in urban dispersion studies

    DEFF Research Database (Denmark)

    Batchvarova, E.; Gryning, Sven-Erik

    2006-01-01

    The present Study addresses recent achievements in better representation Of the urban area structure in meteorology and dispersion parameterisations. The setup and Main Outcome of several recent dispersion experiments in Urban areas and their use in model validation are discussed. The maximum...... BUBBLE Tracer Experiment) the horizontal spread of the plume corresponds to a Lagrangian time scale bigger than the value for ground Sources. Turbulence measurements LIP to 3-5 times the building height Lire needed for direct use in dispersion Calculations....

  10. Nuclear spectroscopic studies. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Bingham, C.R.; Guidry, M.W.; Riedinger, L.L.; Sorensen, S.P.

    1994-02-18

    The Nuclear Physics group at UTK is involved in heavy-ion physics including both nuclear structure and reaction mechanisms. During the last year experimental work has been in 3 broad areas: structure of nuclei at high angular momentum, structure of nuclei far from stability, and ultra-relativistic heavy-ion physics. Results in these areas are described in this document under: properties of high-spin states, study of low-energy levels of nuclei far from stability, and high-energy heavy-ion physics (PHENIX, etc.). Another important component of the work is theoretical interpretation of experimental results (Joint Institute for Heavy Ion Research).

  11. Nuclear spectroscopic studies. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Bingham, C.R.; Guidry, M.W.; Riedinger, L.L.; Sorensen, S.P.

    1993-02-08

    The Nuclear Physics group at the University of Tennessee, Knoxville is involved in several aspects of heavy-ion physics including both nuclear structure and reaction mechanisms. While our main emphasis is on experimental problems involving heavy-ion accelerators, we have maintained a strong collaboration with several theorists in order to best pursue the physics of our measurements. During the last year we have led several experiments at the Holifield Heavy Ion Research Facility and participated in others at Argonne National Laboratory. Also, we continue to be very active in the collaboration to study ultra-relativistic heavy ion physics utilizing the SPS accelerator at CERN in Geneva, Switzerland and in a RHIC detector R&D project. Our experimental work is in four broad areas: (1) the structure of nuclei at high angular momentum, (2) heavy-ion induced transfer reactions, (3) the structure of nuclei far from stability, and (4) ultra-relativistic heavy-ion physics. The results of studies in these particular areas will be described in this document in sections IIA, IIB, IIC, and IID, respectively. Areas (1), (3), and (4) concentrate on the structure of nuclear matter in extreme conditions of rotational motion, imbalance of neutrons and protons, or very high temperature and density. Area (2) pursues the transfer of nucleons to states with high angular momentum, both to learn about their structure and to understand the transfer of particles, energy, and angular momentum in collisions between heavy ions. An important component of our program is the strong emphasis on the theoretical aspects of nuclear structure and reactions.

  12. Longevity studies in GenomEUtwin

    DEFF Research Database (Denmark)

    Skytthe, Axel; Pedersen, Nancy L; Kaprio, Jaakko

    2003-01-01

    for the Danish 1870-1900 twin cohorts to include the new 1901-1910 cohorts, which are consistent with the previous findings. The size of the twin cohorts in GenomEUtwin and the existence of population-based, nationwide health and death registers make epidemiological studies of longevity very powerful...

  13. Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Lænkholm, Anne Vibeke

    step. Our data, contrary to the proposed model of early dissemination of metastatic cells and parallel progression of primary tumors and metastases, provide evidence of linear progression of breast cancer with relatively late dissemination from the primary tumor. The genomic discordance between......Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer...... necessitates knowledge of the degree of genomic concordance between different steps of malignant progression as primary tumors often are used as surrogates of systemic disease. Based on exome sequencing we performed copy number profiling and point mutation detection on successive steps of breast cancer...

  14. Recurrent genomic alterations in sequential progressive leukoplakia and oral cancer: drivers of oral tumorigenesis?

    Science.gov (United States)

    Cervigne, Nilva K; Machado, Jerry; Goswami, Rashmi S; Sadikovic, Bekim; Bradley, Grace; Perez-Ordonez, Bayardo; Galloni, Natalie Naranjo; Gilbert, Ralph; Gullane, Patrick; Irish, Jonathan C; Jurisica, Igor; Reis, Patricia P; Kamel-Reid, Suzanne

    2014-05-15

    A significant proportion (up to 62%) of oral squamous cell carcinomas (OSCCs) may arise from oral potential malignant lesions (OPMLs), such as leukoplakia. Patient outcomes may thus be improved through detection of lesions at a risk for malignant transformation, by identifying and categorizing genetic changes in sequential, progressive OPMLs. We conducted array comparative genomic hybridization analysis of 25 sequential, progressive OPMLs and same-site OSCCs from five patients. Recurrent DNA copy number gains were identified on 1p in 20/25 cases (80%) with minimal, high-level amplification regions on 1p35 and 1p36. Other regions of gains were frequently observed: 11q13.4 (68%), 9q34.13 (64%), 21q22.3 (60%), 6p21 and 6q25 (56%) and 10q24, 19q13.2, 22q12, 5q31.2, 7p13, 10q24 and 14q22 (48%). DNA losses were observed in >20% of samples and mainly detected on 5q31.2 (35%), 16p13.2 (30%), 9q33.1 and 9q33.29 (25%) and 17q11.2, 3p26.2, 18q21.1, 4q34.1 and 8p23.2 (20%). Such copy number alterations (CNAs) were mapped in all grades of dysplasia that progressed, and their corresponding OSCCs, in 70% of patients, indicating that these CNAs may be associated with disease progression. Amplified genes mapping within recurrent CNAs (KHDRBS1, PARP1, RAB1A, HBEGF, PAIP2, BTBD7) were selected for validation, by quantitative real-time PCR, in an independent set of 32 progressive leukoplakia, 32 OSSCs and 21 non-progressive leukoplakia samples. Amplification of BTBD7, KHDRBS1, PARP1 and RAB1A was exclusively detected in progressive leukoplakia and corresponding OSCC. BTBD7, KHDRBS1, PARP1 and RAB1A may be associated with OSCC progression. Protein-protein interaction networks were created to identify possible pathways associated with OSCC progression.

  15. Genome-wide association studies in pediatric chronic kidney disease.

    Science.gov (United States)

    Gupta, Jayanta; Kanetsky, Peter A; Wuttke, Matthias; Köttgen, Anna; Schaefer, Franz; Wong, Craig S

    2016-08-01

    The genome-wide association study (GWAS) has become an established scientific method that provides an unbiased screen for genetic loci potentially associated with phenotypes of clinical interest, such as chronic kidney disease (CKD). Thus, GWAS provides opportunities to gain new perspectives regarding the genetic architecture of CKD progression by identifying new candidate genes and targets for intervention. As such, it has become an important arm of translational science providing a complementary line of investigation to identify novel therapeutics to treat CKD. In this review, we describe the method and the challenges of performing GWAS in the pediatric CKD population. We also provide an overview of successful GWAS for kidney disease, and we discuss the established pediatric CKD cohorts in North America and Europe that are poised to identify genetic risk variants associated with CKD progression.

  16. Progress scored in forest pest studies

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Teaming up with co-workers from State Forestry Administration (SFA), researchers of the CAS Institute of Zoology (IOZ)have scored encouraging progress in their studies of pheromones-based technology against the red turpentine beetle (Dendroctonus valens LeConte).

  17. The multiple facets of homology and their use in comparative genomics to study the evolution of genes, genomes, and species.

    Science.gov (United States)

    Descorps-Declère, Stéphane; Lemoine, Frédéric; Sculo, Quentin; Lespinet, Olivier; Labedan, Bernard

    2008-04-01

    The incredible development of comparative genomics during the last decade has required a correct use of the concept of homology that was previously utilized only by evolutionary biologists. Unhappily, this concept has been often misunderstood and thus misused when exploited outside its evolutionary context. This review brings back to the correct definition of homology and explains how this definition has been progressively refined in order to adapt it to the various new kinds of analysis of gene properties and of their products that appear with the progress of comparative genomics. Then, we illustrate the power and the proficiency of such a concept when using the available genomics data in order to study the evolution of individual genes, of entire genomes and of species, respectively. After explaining how we detect homologues by an exhaustive comparison of a hundred of complete proteomes, we describe three main lines of research we have developed in the recent years. The first one exploits synteny and gene context data to better understand the mechanisms of genome evolution in prokaryotes. The second one is based on phylogenomics approaches to reconstruct the tree of life. The last one is devoted to reminding that protein homology is often limited to structural segments (SOH=segment of homology or module). Detecting and numbering modules allows tracing back protein history by identifying the events of gene duplication and gene fusion. We insist that one of the main present difficulties in such studies is a lack of a reliable method to identify genuine orthologues. Finally, we show how these homology studies are helpful to annotate genes and genomes and to study the complexity of the relationships between sequence and function of a gene.

  18. Human genome libraries. Final progress report, February 1, 1994--August 31, 1997

    Energy Technology Data Exchange (ETDEWEB)

    Kao, Fa-Ten

    1998-01-01

    The goal of this program is to use a novel technology of chromosome microdissection and microcloning to construct chromosome region-specific libraries as resources for various human genome program studies. Region specific libraries have been constructed for the entire human chromosomes 2 and 18.

  19. Effects of curriculum organisation on study progress in engineering studies

    NARCIS (Netherlands)

    van der Hulst, M.; Jansen, E.P.W.A.

    2002-01-01

    Procrastination and time investment are important issues in the study of student performance and progress. Previous research on these issues has mainly concentrated upon individual differences between students in personality and time management skills. However, study progress depends not only on stu

  20. Effects of curriculum organisation on study progress in engineering studies

    NARCIS (Netherlands)

    van der Hulst, M.; Jansen, E.P.W.A.

    2002-01-01

    Procrastination and time investment are important issues in the study of student performance and progress. Previous research on these issues has mainly concentrated upon individual differences between students in personality and time management skills. However, study progress depends not only on stu

  1. Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Lænkholm, Anne Vibeke;

    2015-01-01

    Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer necessita......Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer...... progression from one breast cancer patient, including two different regions of Ductal Carcinoma In Situ (DCIS), primary tumor and an asynchronous metastasis. We identify a remarkable landscape of somatic mutations, retained throughout breast cancer progression and with new mutational events emerging at each...

  2. Application of genomics-assisted breeding for generation of climate resilient crops: Progress and prospects

    Directory of Open Access Journals (Sweden)

    Chittaranjan eKole

    2015-08-01

    Full Text Available Climate change affects agricultural productivity worldwide. Increased prices of food commodities are the initial indication of drastic edible yield loss, which is expected to surge further due to global warming. This situation has compelled plant scientists to develop climate change-resilient crops, which can withstand broad-spectrum stresses such as drought, heat, cold, salinity, flood and submergence, and pests along with increased productivity. Genomics appears to be a promising tool for deciphering the stress responsiveness of crop species with adaptation traits or in wild relatives towards identifying underlying genes, alleles or quantitative trait loci. Molecular breeding approaches have been proven helpful in enhancing the stress adaptation of crop plants, and recent advancement in next-generation sequencing along with high-throughput sequencing and phenotyping platforms have transformed molecular breeding to genomics-assisted breeding (GAB. In view of this, the present review elaborates the progress and prospects of GAB in improving climate change resilience in crop plants towards circumventing global food insecurity.

  3. Genomics of Ovarian Cancer Progression Reveals Diverse Metastatic Trajectories Including Intraepithelial Metastasis to the Fallopian Tube.

    Science.gov (United States)

    Eckert, Mark A; Pan, Shawn; Hernandez, Kyle M; Loth, Rachel M; Andrade, Jorge; Volchenboum, Samuel L; Faber, Pieter; Montag, Anthony; Lastra, Ricardo; Peter, Marcus E; Yamada, S Diane; Lengyel, Ernst

    2016-12-01

    Accumulating evidence has supported the fallopian tube rather than the ovary as the origin for high-grade serous ovarian cancer (HGSOC). To understand the relationship between putative precursor lesions and metastatic tumors, we performed whole-exome sequencing on specimens from eight HGSOC patient progression series consisting of serous tubal intraepithelial carcinomas (STIC), invasive fallopian tube lesions, invasive ovarian lesions, and omental metastases. Integration of copy number and somatic mutations revealed patient-specific patterns with similar mutational signatures and copy-number variation profiles across all anatomic sites, suggesting that genomic instability is an early event in HGSOC. Phylogenetic analyses supported STIC as precursor lesions in half of our patient cohort, but also identified STIC as metastases in 2 patients. Ex vivo assays revealed that HGSOC spheroids can implant in the fallopian tube epithelium and mimic STIC lesions. That STIC may represent metastases calls into question the assumption that STIC are always indicative of primary fallopian tube cancers. We find that the putative precursor lesions for HGSOC, STIC, possess most of the genomic aberrations present in advanced cancers. In addition, a proportion of STIC represent intraepithelial metastases to the fallopian tube rather than the origin of HGSOC. Cancer Discov; 6(12); 1342-51. ©2016 AACR.See related commentary by Swisher et al., p. 1309This article is highlighted in the In This Issue feature, p. 1293. ©2016 American Association for Cancer Research.

  4. Sinbase: an integrated database to study genomics, genetics and comparative genomics in Sesamum indicum.

    Science.gov (United States)

    Wang, Linhai; Yu, Jingyin; Li, Donghua; Zhang, Xiurong

    2015-01-01

    Sesame (Sesamum indicum L.) is an ancient and important oilseed crop grown widely in tropical and subtropical areas. It belongs to the gigantic order Lamiales, which includes many well-known or economically important species, such as olive (Olea europaea), leonurus (Leonurus japonicus) and lavender (Lavandula spica), many of which have important pharmacological properties. Despite their importance, genetic and genomic analyses on these species have been insufficient due to a lack of reference genome information. The now available S. indicum genome will provide an unprecedented opportunity for studying both S. indicum genetic traits and comparative genomics. To deliver S. indicum genomic information to the worldwide research community, we designed Sinbase, a web-based database with comprehensive sesame genomic, genetic and comparative genomic information. Sinbase includes sequences of assembled sesame pseudomolecular chromosomes, protein-coding genes (27,148), transposable elements (372,167) and non-coding RNAs (1,748). In particular, Sinbase provides unique and valuable information on colinear regions with various plant genomes, including Arabidopsis thaliana, Glycine max, Vitis vinifera and Solanum lycopersicum. Sinbase also provides a useful search function and data mining tools, including a keyword search and local BLAST service. Sinbase will be updated regularly with new features, improvements to genome annotation and new genomic sequences, and is freely accessible at http://ocri-genomics.org/Sinbase/.

  5. Potential assessment of genome-wide association study and genomic selection in Japanese pear Pyrus pyrifolia

    OpenAIRE

    Iwata, Hiroyoshi; Hayashi, Takeshi; Terakami, Shingo; Takada, Norio; Sawamura, Yutaka; Yamamoto, Toshiya

    2013-01-01

    Although the potential of marker-assisted selection (MAS) in fruit tree breeding has been reported, bi-parental QTL mapping before MAS has hindered the introduction of MAS to fruit tree breeding programs. Genome-wide association studies (GWAS) are an alternative to bi-parental QTL mapping in long-lived perennials. Selection based on genomic predictions of breeding values (genomic selection: GS) is another alternative for MAS. This study examined the potential of GWAS and GS in pear breeding w...

  6. Progress in unraveling the genetic etiology of Parkinson disease in a genomic era.

    Science.gov (United States)

    Verstraeten, Aline; Theuns, Jessie; Van Broeckhoven, Christine

    2015-03-01

    Parkinson disease (PD) and Parkinson-plus syndromes are genetically heterogeneous neurological diseases. Initial studies into the genetic causes of PD relied on classical molecular genetic approaches in well-documented case families. More recently, these approaches have been combined with exome sequencing and together have identified 15 causal genes. Additionally, genome-wide association studies (GWASs) have discovered over 25 genetic risk factors. Elucidation of the genetic architecture of sporadic and familial parkinsonism, however, has lagged behind that of simple Mendelian conditions, suggesting the existence of features confounding genetic data interpretation. Here we discuss the successes and potential pitfalls of gene discovery in PD and related disorders in the post-genomic era. With an estimated 30% of trait variance currently unexplained, tackling current limitations will further expedite gene discovery and lead to increased application of these genetic insights in molecular diagnostics using gene panel and exome sequencing strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Research Progress of Sugarcane Chloroplast Genome%甘蔗叶绿体基因组研究进展

    Institute of Scientific and Technical Information of China (English)

    吴杨; 周会

    2013-01-01

    Along with the development of modern molecular biology technologies, complete chloroplast genomes have been sequenced in various plant species to date, and the structure, function and expression of these genes have been deter-mined. The chloroplast genome structure in most higher plants is stable, since the gene number, arrangement and composition are conservative. The determination of sugarcane chloroplast genome sequence laid a good foundation for sugarcane chloroplast related research. This article gives a review on the research progress of sugarcane chloroplast genome through the chloroplast genome map, gene structure, function, chloroplast RNA editing, and phylogenetic analysis in Saccharum and relat-ed genera. This study held great potential to clarify more directions in researches, including sugarcane chloroplast genetic transformation, complete chloroplast nu-cleotide sequence determination in Saccharum and closely related genera, cpSSRs development and application.%随着现代分子生物学技术的发展,目前已经完成了多种植物叶绿体基因组的全序列测定,并研究了这些基因的结构、功能与表达。大部分高等植物的叶绿体基因组结构稳定,基因数量、排列顺序及组成上具有保守性。甘蔗叶绿体基因组测序工作的完成为甘蔗叶绿体相关研究奠定了良好基础。文章从甘蔗叶绿体基因组图谱、结构和功能基因、叶绿体RNA编辑以及甘蔗属叶绿体系统进化等方面综合概述了甘蔗叶绿体基因组研究取得的成果,并从甘蔗叶绿体遗传转化、甘蔗及近缘属叶绿体基因组测序和叶绿体基因组 cpSSRs开发利用等方面指出甘蔗叶绿体基因组今后的研究方向。

  8. Draft Genome Sequences of Two Propionibacterium acnes Strains Isolated from Progressive Macular Hypomelanosis Lesions of Human Skin

    DEFF Research Database (Denmark)

    Petersen, Rolf; Lomholt, Hans B.; Scholz, Christian F. P.;

    2015-01-01

    Propionibacterium acnes is a Gram-positive bacterium that is prevalent on human skin. It has been associated with skin disorders such as acne vulgaris and progressive macular hypomelanosis (PMH). Here, we report draft genome sequences of two type III P. acnes strains, PMH5 and PMH7, isolated from...

  9. Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Lænkholm, Anne-Vibeke

    2015-01-01

    Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer necessita...

  10. Draft Genome Sequences of Two Propionibacterium acnes Strains Isolated from Progressive Macular Hypomelanosis Lesions of Human Skin

    DEFF Research Database (Denmark)

    Petersen, Rolf; Lomholt, Hans B.; Scholz, Christian F. P.

    2015-01-01

    Propionibacterium acnes is a Gram-positive bacterium that is prevalent on human skin. It has been associated with skin disorders such as acne vulgaris and progressive macular hypomelanosis (PMH). Here, we report draft genome sequences of two type III P. acnes strains, PMH5 and PMH7, isolated from...

  11. Progress with vegetation studies in South Africa

    Directory of Open Access Journals (Sweden)

    J. C. Scheepers

    1983-12-01

    Full Text Available Vegetation studies at various levels of detail and using various methods are briefly reviewed. The approach and procedures of the Zurich-Montpellier school of phytosociology as a standard methodology for regional studies has become increasingly recognized. Progress has been made in regional studies in the fynbos and woodland biomes. but grassland, forest and karoo vegetation have been much neglected. There have also been marked increases in activity over a wide range of additional vegetation studies including new fields of research, particularly ecosystem studies. However, there are still vast gaps in our knowledge of the basic vegetationa! resources of the country. A systematic regional-study programme is being launched to remedy these deficiencies in fundamental knowledge.

  12. Coordination: southeast continental shelf studies. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Menzel, D.W.

    1980-03-01

    The GABEX I experiment is designed to provide synoptic coverage of a series of Gulf Stream wave-like disturbances, the effect of these on the circulation of the entire shelf, and on biological and chemical processes. This study was initiated in February 1980 when current meter arrays were deployed. These meters will be removed in July 1980. In April three ships will simultaneously study the effects of Gulf Stream disturbances on the hydrography, chemistry, and biology of the shelf. One vessel will track a specific wave-like disturbance and provide synoptic coverage of the shelf area. The second vessel will determine the effect of shelf break processes on adjacent shelf water; and the third will study trace metal distributions in and outside of disturbances. Research progress is reported in continental shelf studies, nearshore and estuarine studies (diffusion of freshwater out of nearshore zone), tidal currents and material transport, and mixing of inlet plumes.

  13. Progress and knowledge gaps in Culicoides genetics, genomics and population modelling: 2003 to 2014.

    Science.gov (United States)

    Carpenter, Simon

    2016-09-30

    In the 10 years, since the last international meeting on Bluetongue virus (BTV) and related Orbiviruses in Sicily, there have been huge advances in explorations of the genetics and genomics of Culicoides, culminating in the imminent release of the rst full genome de novo assembly for the genus. In parallel, mathematical models used to predict Culicoides adult distribution, seasonality, and dispersal have also increased in sophistication, re ecting advances in available computational power and expertise. While these advances have focused upon the outbreaks of BTV in Europe, there is an opportunity to extend these techniques to other regions as part of global studies of the genus. This review takes a selective approach to examining the past decade of research in these areas and provides a personal viewpoint of future directions of research that may prove productive.

  14. Progress of Solar Corona Study in China

    Institute of Scientific and Technical Information of China (English)

    ZHAO Xinhua; SONG Wenbin

    2008-01-01

    Solar corona study is an important aspect of space weather research.In recent years,great achieVements have been acquired on the solar corona study by the space physics group of China.This paper gives a brief outline of these progresses that have been made during 2006--2008.This kind of research includes observational study of the corona,theoretical investigations,statistical analysis based on a large number of data sets,numerical method for MHD modeling,numerical study of space weather events,and prediction methods for the complicated processes originating from the solar corona.Each is given as a separate part in the following.

  15. Dual Roles of RNF2 in Melanoma Progression | Office of Cancer Genomics

    Science.gov (United States)

    Epigenetic regulators have emerged as critical factors governing the biology of cancer. Here, in the context of melanoma, we show that RNF2 is prognostic, exhibiting progression-correlated expression in human melanocytic neoplasms. Through a series of complementary gain-of-function and loss-of-function studies in mouse and human systems, we establish that RNF2 is oncogenic and prometastatic.

  16. Chicken's Genome Decoded

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ After completing the work on mapping chicken genome sequence and chicken genome variation in early March, 2004, two international research consortiums have made significant progress in reading the maps, shedding new light on the studies into the first bird as well as the first agricultural animal that has its genome sequenced and analyzed in the world.

  17. Studies in developmental immunogenetics. Annual progress report

    Energy Technology Data Exchange (ETDEWEB)

    Owen, R D

    1976-05-26

    Progress is reported on studies of genetic regulation, mainly in complex organisms, and with an emphasis on the immune system as a model for developmental analysis and as a tool for following the development of other systems, especially the brain. Results are reported from studies of biochemical genetics, primarily from a developmental viewpoint and with particular regard to defense mechanisms; cellular aspects of the immune system; the area of cancer immunology and cell specificities as related to tumor systems, primarily from an immunogenetic viewpoint and with particular reference to leukemias in the mouse; and the disruptions of genetic control mechanisms in tumor development, especially as approached through the reappearance of fetal antigens associated with tumor development.

  18. Current progress in the biology of members of the Sporothrix schenckii complex following the genomic era.

    Science.gov (United States)

    Mora-Montes, Héctor M; Dantas, Alessandra da Silva; Trujillo-Esquivel, Elías; de Souza Baptista, Andrea R; Lopes-Bezerra, Leila M

    2015-09-01

    Sporotrichosis has been attributed for more than a century to one single etiological agent, Sporothrix schencki. Only eight years ago, it was described that, in fact, the disease is caused by several pathogenic cryptic species. The present review will focus on recent advances to understand the biology and virulence of epidemiologically relevant pathogenic species of the S. schenckii complex. The main subjects covered are the new clinical and epidemiological aspects including diagnostic and therapeutic challenges, the development of molecular tools, the genome database and the perspectives for study of virulence of emerging Sporothrix species.

  19. Patterns of progression, treatment of progressive disease and post-progression survival in the New EPOC study.

    Science.gov (United States)

    Pugh, Siân A; Bowers, Megan; Ball, Alexandre; Falk, Stephen; Finch-Jones, Meg; Valle, Juan W; O'Reilly, Derek A; Siriwardena, Ajith K; Hornbuckle, Joanne; Rees, Myrddin; Rees, Charlotte; Iveson, Tim; Hickish, Tamas; Maishman, Tom; Stanton, Louise; Dixon, Elizabeth; Corkhill, Andrea; Radford, Mike; Garden, O James; Cunningham, David; Maughan, Tim S; Bridgewater, John A; Primrose, John N

    2016-08-09

    The addition of cetuximab (CTX) to perioperative chemotherapy (CT) for operable colorectal liver metastases resulted in a shorter progression-free survival. Details of disease progression are described to further inform the primary study outcome. A total of 257 KRAS wild-type patients were randomised to CT alone or CT with CTX. Data regarding sites and treatment of progressive disease were obtained for the 109 (CT n=48, CT and CTX n=61) patients with progressive disease at the cut-off date for analysis of November 2012. The liver was the most frequent site of progression (CT 67% (32/48); CT and CTX 66% (40/61)). A higher proportion of patients in the CT and group had multiple sites of progressive disease (CT 8%, 4/48; CT and CTX 23%, 14/61 P=0.04). Further treatment for progressive disease is known for 84 patients of whom 69 received further CT, most frequently irinotecan based. Twenty-two patients, 11 in each arm, received CTX as a further line agent. Both the distribution of progressive disease and further treatment are as expected for such a cohort. The pattern of disease progression seen is consistent with failure of systemic micrometastatic disease control rather than failure of local disease control following liver surgery.

  20. Identification of novel genomic markers related to progression to glioblastoma through genomic profiling of 25 primary glioma cell lines.

    NARCIS (Netherlands)

    Roversi, G.; Pfundt, R.; Moroni, R.F.; Magnani, I.; Reijmersdal, S.V. van; Pollo, B.; Straatman, H.M.P.M.; Larizza, L.; Schoenmakers, E.F.P.M.

    2006-01-01

    Identification of genetic copy number changes in glial tumors is of importance in the context of improved/refined diagnostic, prognostic procedures and therapeutic decision-making. In order to detect recurrent genomic copy number changes that might play a role in glioma pathogenesis and/or progressi

  1. A Gene Gravity Model for the Evolution of Cancer Genomes: A Study of 3,000 Cancer Genomes across 9 Cancer Types

    Science.gov (United States)

    Lin, Chen-Ching; Zhao, Junfei; Jia, Peilin; Li, Wen-Hsiung; Zhao, Zhongming

    2015-01-01

    Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation) alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1). The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation density at the genome level compared to the wild-type groups. Furthermore, we provided statistical evidence that hypermutation of cancer driver genes on inactive X chromosomes is a general feature in female cancer genomes. In summary, this study sheds light on the functional consequences and evolutionary characteristics of somatic mutations during tumorigenesis by propelling adaptive cancer genome evolution, which would provide new perspectives for cancer research and therapeutics. PMID:26352260

  2. A Gene Gravity Model for the Evolution of Cancer Genomes: A Study of 3,000 Cancer Genomes across 9 Cancer Types.

    Directory of Open Access Journals (Sweden)

    Feixiong Cheng

    2015-09-01

    Full Text Available Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1. The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation density at the genome level compared to the wild-type groups. Furthermore, we provided statistical evidence that hypermutation of cancer driver genes on inactive X chromosomes is a general feature in female cancer genomes. In summary, this study sheds light on the functional consequences and evolutionary characteristics of somatic mutations during tumorigenesis by propelling adaptive cancer genome evolution, which would provide new perspectives for cancer research and therapeutics.

  3. Appearance traits in fish farming: progress from classical genetics to genomics, providing insight into current and potential genetic improvement

    Science.gov (United States)

    Colihueque, Nelson; Araneda, Cristian

    2014-01-01

    Appearance traits in fish, those external body characteristics that influence consumer acceptance at point of sale, have come to the forefront of commercial fish farming, as culture profitability is closely linked to management of these traits. Appearance traits comprise mainly body shape and skin pigmentation. Analysis of the genetic basis of these traits in different fish reveals significant genetic variation within populations, indicating potential for their genetic improvement. Work into ascertaining the minor or major genes underlying appearance traits for commercial fish is emerging, with substantial progress in model fish in terms of identifying genes that control body shape and skin colors. In this review, we describe research progress to date, especially with regard to commercial fish, and discuss genomic findings in model fish in order to better address the genetic basis of the traits. Given that appearance traits are important in commercial fish, the genomic information related to this issue promises to accelerate the selection process in coming years. PMID:25140172

  4. Progress on Transferring Elite Genes from Non-AA Genome Wild Rice into Oryza sativa through Interspecific Hybridization

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The progress of research on transferring elite genes from non-AA genome wild rice into Oryza sativa through interspecific hybridization are in three respects,that is,breeding monosomic alien addition lines (MAALs),constructing introgression lines (ILs) and analyzing the heredity of the characters and mapping the related genes.There are serious reproductive barriers,mainly incrossability and hybrid sterility,in the interspecific hybridization of O.sativa with non-AA genome wild rice.These are the 'bottleneck' for transferring elite genes from wild rice to O.sativa.Combining traditional crossing method with biotechnique is a reliable way to overcome the reproductive barriers and to improve the utilizing efficiency of non-AA genome wild rice.

  5. High-resolution array comparative genomic hybridization of chromosome 8q: evaluation of putative progression markers for gastroesophageal junction adenocarcinomas.

    Science.gov (United States)

    van Duin, M; van Marion, R; Vissers, K J; Hop, W C J; Dinjens, W N M; Tilanus, H W; Siersema, P D; van Dekken, H

    2007-01-01

    Amplification of 8q is frequently found in gastroesophageal junction (GEJ) cancer. It is usually detected in high-grade, high-stage GEJ adenocarcinomas. Moreover, it has been implicated in tumor progression in other cancer types. In this study, a detailed genomic analysis of 8q was performed on a series of GEJ adenocarcinomas, including 22 primary adenocarcinomas, 13 cell lines and two xenografts, by array comparative genomic hybridization (aCGH) with a whole chromosome 8q contig array. Of the 37 specimens, 21 originated from the esophagus and 16 were derived from the gastric cardia. Commonly overrepresented regions were identified at distal 8q, i.e. 124-125 Mb (8q24.13), at 127-128 Mb (8q24.21), and at 141-142 Mb (8q24.3). From these regions six genes were selected with putative relevance to cancer: ANXA13, MTSS1, FAM84B (alias NSE2), MYC, C8orf17 (alias MOST-1) and PTK2 (alias FAK). In addition, the gene EXT1 was selected since it was found in a specific amplification in cell line SK-GT-5. Quantitative RT-PCR analysis of these seven genes was subsequently performed on a panel of 24 gastroesophageal samples, including 13 cell lines, two xenografts and nine normal stomach controls. Significant overexpression was found for MYC and EXT1 in GEJ adenocarcinoma cell lines and xenografts compared to normal controls. Expression of the genes MTSS1, FAM84B and C8orf17 was found to be significantly decreased in this set of cell lines and xenografts. We conclude that, firstly, there are other genes than MYC involved in the 8q amplification in GEJ cancer. Secondly, the differential expression of these genes contributes to unravel the biology of GEJ adenocarcinomas.

  6. Progress on the CLIC Linear Collider Study

    CERN Document Server

    Guignard, Gilbert

    2001-01-01

    The CLIC study aims at a multi-TeV, high luminosity e+e- linear collider design. Beam acceleration uses high frequency (30 GHz), normal conducting structures operating at high accelerating gradients, in order to reduce the length and, in consequence, the cost of the linac. The cost-effective RF power production scheme, based on the so-called Two-beam Acceleration method, enables electrons and positrons to be collided at energies ranging from ~ 0.1 TeV up to a maximum of 5 TeV, in stages. A road map has been drawn up to indicate the research and development necessary to demonstrate the technical feasibility of a 3 TeV centre-of-mass collider with a luminosity of 1035 cm-2s-1. Considerable progress has been made in meeting the challenges associated with the CLIC technology and the present paper briefly reviews some of them. In particular, the status is given of the studies on the CLIC high-gradient structures, the dynamic time-dependent effects, the stabilisation of the vibration and the beam delivery system. T...

  7. Study of heavy flavored particles. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    1991-12-31

    This report discusses progress on the following topics: time-of- flight system; charmed baryon production and decays; D decays to baryons; measurement of sigma plus particles magnetic moments; and strong interaction coupling. (LSP)

  8. Progress in octahedral spherical hohlraum study

    Directory of Open Access Journals (Sweden)

    Ke Lan

    2016-01-01

    Full Text Available In this paper, we give a review of our theoretical and experimental progress in octahedral spherical hohlraum study. From our theoretical study, the octahedral spherical hohlraums with 6 Laser Entrance Holes (LEHs of octahedral symmetry have robust high symmetry during the capsule implosion at hohlraum-to-capsule radius ratio larger than 3.7. In addition, the octahedral spherical hohlraums also have potential superiority on low backscattering without supplementary technology. We studied the laser arrangement and constraints of the octahedral spherical hohlraums, and gave a design on the laser arrangement for ignition octahedral hohlraums. As a result, the injection angle of laser beams of 50°–60° was proposed as the optimum candidate range for the octahedral spherical hohlraums. We proposed a novel octahedral spherical hohlraum with cylindrical LEHs and LEH shields, in order to increase the laser coupling efficiency and improve the capsule symmetry and to mitigate the influence of the wall blowoff on laser transport. We studied on the sensitivity of the octahedral spherical hohlraums to random errors and compared the sensitivity among the octahedral spherical hohlraums, the rugby hohlraums and the cylindrical hohlraums, and the results show that the octahedral spherical hohlraums are robust to these random errors while the cylindrical hohlraums are the most sensitive. Up till to now, we have carried out three experiments on the spherical hohlraum with 2 LEHs on Shenguang(SG laser facilities, including demonstration of improving laser transport by using the cylindrical LEHs in the spherical hohlraums, spherical hohlraum energetics on the SGIII prototype laser facility, and comparisons of laser plasma instabilities between the spherical hohlraums and the cylindrical hohlraums on the SGIII laser facility.

  9. Current status and prospects for the study of Nicotiana genomics, genetics, and nicotine biosynthesis genes.

    Science.gov (United States)

    Wang, Xuewen; Bennetzen, Jeffrey L

    2015-02-01

    Nicotiana, a member of the Solanaceae family, is one of the most important research model plants, and of high agricultural and economic value worldwide. To better understand the substantial and rapid research progress with Nicotiana in recent years, its genomics, genetics, and nicotine gene studies are summarized, with useful web links. Several important genetic maps, including a high-density map of N. tabacum consisting of ~2,000 markers published in 2012, provide tools for genetics research. Four whole genome sequences are from allotetraploid species, including N. benthamiana in 2012, and three N. tabacum cultivars (TN90, K326, and BX) in 2014. Three whole genome sequences are from diploids, including progenitors N. sylvestris and N. tomentosiformis in 2013 and N. otophora in 2014. These and additional studies provide numerous insights into genome evolution after polyploidization, including changes in gene composition and transcriptome expression in N. tabacum. The major genes involved in the nicotine biosynthetic pathway have been identified and the genetic basis of the differences in nicotine levels among Nicotiana species has been revealed. In addition, other progress on chloroplast, mitochondrial, and NCBI-registered projects on Nicotiana are discussed. The challenges and prospects for genomic, genetic and application research are addressed. Hence, this review provides important resources and guidance for current and future research and application in Nicotiana.

  10. 2012 U.S. Department of Energy: Joint Genome Institute: Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, David [DOE JGI Public Affairs Manager

    2013-01-01

    The mission of the U.S. Department of Energy Joint Genome Institute (DOE JGI) is to serve the diverse scientific community as a user facility, enabling the application of large-scale genomics and analysis of plants, microbes, and communities of microbes to address the DOE mission goals in bioenergy and the environment. The DOE JGI's sequencing efforts fall under the Eukaryote Super Program, which includes the Plant and Fungal Genomics Programs; and the Prokaryote Super Program, which includes the Microbial Genomics and Metagenomics Programs. In 2012, several projects made news for their contributions to energy and environment research.

  11. [A review of the genomic and gene cloning studies in trees].

    Science.gov (United States)

    Yin, Tong-Ming

    2010-07-01

    Supported by the Department of Energy (DOE) of U.S., the first tree genome, black cottonwood (Populus trichocarpa), has been completely sequenced and publicly release. This is the milestone that indicates the beginning of post-genome era for forest trees. Identification and cloning genes underlying important traits are one of the main tasks for the post-genome-era tree genomic studies. Recently, great achievements have been made in cloning genes coordinating important domestication traits in some crops, such as rice, tomato, maize and so on. Molecular breeding has been applied in the practical breeding programs for many crops. By contrast, molecular studies in trees are lagging behind. Trees possess some characteristics that make them as difficult organisms for studying on locating and cloning of genes. With the advances in techniques, given also the fast growth of tree genomic resources, great achievements are desirable in cloning unknown genes from trees, which will facilitate tree improvement programs by means of molecular breeding. In this paper, the author reviewed the progress in tree genomic and gene cloning studies, and prospected the future achievements in order to provide a useful reference for researchers working in this area.

  12. Utilization of complete chloroplast genomes for phylogenetic studies

    NARCIS (Netherlands)

    Ramlee, Shairul Izan Binti

    2016-01-01

    Chloroplast DNA sequence polymorphisms are a primary source of data in many plant phylogenetic studies. The chloroplast genome is relatively conserved in its evolution making it an ideal molecule to retain phylogenetic signals. The chloroplast genome is also largely, but not completely, free from ot

  13. Data management for genomic mapping applications: A case study

    Energy Technology Data Exchange (ETDEWEB)

    Markowitz, V.M.; Lewis, S.; McCarthy, J.; Olken, F.; Zorn, M.

    1992-05-01

    In this paper we describe a new approach to the construction of data management systems for genomic mapping applications in molecular biology, genetics, and plant breeding. We discuss the architecture of such systems and propose an incremental approach to the development of such systems. We illustrate the proposed approach and architecture with a case study of a prototype data management system for genomic maps.

  14. Cancer genetic association studies in the genome-wide age

    OpenAIRE

    Savage, Sharon A

    2008-01-01

    Genome-wide association studies of hundreds of thousands of SNPs have led to a deluge of studies of genetic variation in cancer and other common diseases. Large case–control and cohort studies have identified novel SNPs as markers of cancer risk. Genome-wide association study SNP data have also advanced understanding of population-specific genetic variation. While studies of risk profiles, combinations of SNPs that may increase cancer risk, are not yet clinically applicable, future, large-sca...

  15. Progress of Study on Chlamydial Pathogenesis

    Institute of Scientific and Technical Information of China (English)

    刘全中; 傅宜志; 陈锦英

    2001-01-01

    Chlamydia, a human pathogen that mediates chronic, persistent and repeated infection progress, is capable of inflicting permanent scar formation. A typical reticular body is found in persistent infections. Chlamydial Hsp 60, interferon(IFN) -gamma and other cytokines function in the course of repeated infection. Immunopathological factors mediate chronic infection.

  16. The Global Invertebrate Genomics Alliance (GIGA): Developing Community Resources to Study Diverse Invertebrate Genomes

    KAUST Repository

    Bracken-Grissom, Heather

    2013-12-12

    Over 95% of all metazoan (animal) species comprise the invertebrates, but very few genomes from these organisms have been sequenced. We have, therefore, formed a Global Invertebrate Genomics Alliance (GIGA). Our intent is to build a collaborative network of diverse scientists to tackle major challenges (e.g., species selection, sample collection and storage, sequence assembly, annotation, analytical tools) associated with genome/transcriptome sequencing across a large taxonomic spectrum. We aim to promote standards that will facilitate comparative approaches to invertebrate genomics and collaborations across the international scientific community. Candidate study taxa include species from Porifera, Ctenophora, Cnidaria, Placozoa, Mollusca, Arthropoda, Echinodermata, Annelida, Bryozoa, and Platyhelminthes, among others. GIGA will target 7000 noninsect/nonnematode species, with an emphasis on marine taxa because of the unrivaled phyletic diversity in the oceans. Priorities for selecting invertebrates for sequencing will include, but are not restricted to, their phylogenetic placement; relevance to organismal, ecological, and conservation research; and their importance to fisheries and human health. We highlight benefits of sequencing both whole genomes (DNA) and transcriptomes and also suggest policies for genomic-level data access and sharing based on transparency and inclusiveness. The GIGA Web site () has been launched to facilitate this collaborative venture.

  17. Reactive oxygen species, DNA damage, and error-prone repair: a model for genomic instability with progression in myeloid leukemia?

    Science.gov (United States)

    Rassool, Feyruz V; Gaymes, Terry J; Omidvar, Nader; Brady, Nicola; Beurlet, Stephanie; Pla, Marika; Reboul, Murielle; Lea, Nicholas; Chomienne, Christine; Thomas, Nicholas S B; Mufti, Ghulam J; Padua, Rose Ann

    2007-09-15

    Myelodysplastic syndromes (MDS) comprise a heterogeneous group of disorders characterized by ineffective hematopoiesis, with an increased propensity to develop acute myelogenous leukemia (AML). The molecular basis for MDS progression is unknown, but a key element in MDS disease progression is loss of chromosomal material (genomic instability). Using our two-step mouse model for myeloid leukemic disease progression involving overexpression of human mutant NRAS and BCL2 genes, we show that there is a stepwise increase in the frequency of DNA damage leading to an increased frequency of error-prone repair of double-strand breaks (DSB) by nonhomologous end-joining. There is a concomitant increase in reactive oxygen species (ROS) in these transgenic mice with disease progression. Importantly, RAC1, an essential component of the ROS-producing NADPH oxidase, is downstream of RAS, and we show that ROS production in NRAS/BCL2 mice is in part dependent on RAC1 activity. DNA damage and error-prone repair can be decreased or reversed in vivo by N-acetyl cysteine antioxidant treatment. Our data link gene abnormalities to constitutive DNA damage and increased DSB repair errors in vivo and provide a mechanism for an increase in the error rate of DNA repair with MDS disease progression. These data suggest treatment strategies that target RAS/RAC pathways and ROS production in human MDS/AML.

  18. Using CAVE technology for functional genomics studies.

    Science.gov (United States)

    Sensen, Christoph W

    2002-01-01

    We have established the first Java 3D-enabled CAVE (CAVE automated virtual environment). The Java application programming interface allows the complete separation of the program development from the program execution, opening new application domains for the CAVE technology. Programs can be developed on any Java-enabled computer platform, including Windows, Macintosh, and Linux workstations, and executed in the CAVE without modification. The introduction of Java, one of the major programming environments for bioinformatics, into the CAVE environment allows the rapid development applications for genome research, especially for the analysis of the spatial and temporal data that are being produced by functional genomics experiments. The CAVE technology will play a major role in the modeling of biological systems that is necessary to understand how these systems are organized and how they function.

  19. Progress in the studies of photoelectrochemical sensors

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Photoelectrochemical sensor is a new kind of developing analytical device based on the photoelectrochemical properties of materials.Because of its remarkable sensitivity,inherent miniaturization,portability and easy integration,photoelectrochemical analysis is becoming a promising analytical technique.This review focuses on the basic principles,classification,characteristics,and research progress of photoelectrochemical sensors with 94 references.The prospect of the development of photoelectrochemical sensors is also evaluated and discussed.

  20. Azolla - A Model Organism for Plant Genomic Studies

    Institute of Scientific and Technical Information of China (English)

    Yin-Long Qiu; Jun Yu

    2003-01-01

    The aquatic ferns of the genus Azolla are nitrogen-fixing plants that have great potentials in agricultural production and environmental conservation. Azolla in many aspects is qualified to serve as a model organism for genomic studies because of its importance in agriculture, its unique position in plant evolution, its symbiotic relationship with the N2-fixing cyanobacterium, Anabaena azollae, and its moderate-sized genome. The goals of this genome project are not only to understand the biology of the Azolla genome to promote its applications in biological research and agriculture practice but also to gain critical insights about evolution of plant genomes. Together with the strategic and technical improvement as well as cost reduction of DNA sequencing, the deciphering of their genetic code is imminent.

  1. Azolla—A Model Organism for Plant Genomic Studies

    Institute of Scientific and Technical Information of China (English)

    Yin-LongQiu; JunYu

    2003-01-01

    The aquatic ferns of the genus Azolla are nitrogen-fixing plants that have great potentials in agricultural production and environmental conservation.Azolla in many aspects is qualified to serve as a model organism for genomic studies because of its importance in agriculture,its unique position in plant evolution,its symbiotic relationship with the N2-fixing cyanobacterium,Anabaena azollae,and its moderate-sized genome.The goals of this genome project are not only to understand the biology of the Azolla genome to promote its applications in biological research and agriculture practice but also to gain critical insights about evolution of plant genomes.Together with the strategic and technical improvement as well as cost reduction of DNA sequencing,the deciphering of their genetic code is imminent.

  2. Genome-Based Studies of Marine Microorganisms to Maximize the Diversity of Natural Products Discovery for Medical Treatments

    Directory of Open Access Journals (Sweden)

    Xin-Qing Zhao

    2011-01-01

    Full Text Available Marine microorganisms are rich source for natural products which play important roles in pharmaceutical industry. Over the past decade, genome-based studies of marine microorganisms have unveiled the tremendous diversity of the producers of natural products and also contributed to the efficiency of harness the strain diversity and chemical diversity, as well as the genetic diversity of marine microorganisms for the rapid discovery and generation of new natural products. In the meantime, genomic information retrieved from marine symbiotic microorganisms can also be employed for the discovery of new medical molecules from yet-unculturable microorganisms. In this paper, the recent progress in the genomic research of marine microorganisms is reviewed; new tools of genome mining as well as the advance in the activation of orphan pathways and metagenomic studies are summarized. Genome-based research of marine microorganisms will maximize the biodiscovery process and solve the problems of supply and sustainability of drug molecules for medical treatments.

  3. Experimental genomics: The application of DNA microarrays in cellular and molecular biology studies

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The genome sequence information in combination with DNA microarrays promises to revolutionize the way of cellular and molecular biological research by allowing complex mixtures of RNA and DNA to interrogated in a parallel and quant itative fashion. DNA microarrays can be used to measure levels of gene expressio n for tens of thousands of gene simultaneously and take advantage of all availab le sequence information for experimental design and data interpretation in pursu it of biological understanding. Recent progress in experimental genomics allows DNA microarrays not simply to provide a catalogue of all the genes and informati on about their function, but to understand how the components work together to comprise functioning cells and organisms. This brief review gives a survey of DNA microarrays technology and its applications in genome and gene function analysis, gene expression studies, biological signal and defense system, cell cyclereg ulation, mechanism of transcriptional regulation, proteomics, and the functional ity of food component.

  4. Integrated Genome-Based Studies of Shewanella Ecophysiology

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jizhong; He, Zhili

    2014-04-08

    As a part of the Shewanella Federation project, we have used integrated genomic, proteomic and computational technologies to study various aspects of energy metabolism of two Shewanella strains from a systems-level perspective.

  5. Genome-wide association study of clinical dimensions of schizophrenia

    DEFF Research Database (Denmark)

    Fanous, Ayman H; Zhou, Baiyu; Aggen, Steven H;

    2012-01-01

    Multiple sources of evidence suggest that genetic factors influence variation in clinical features of schizophrenia. The authors present the first genome-wide association study (GWAS) of dimensional symptom scores among individuals with schizophrenia....

  6. Mycobacterial species as case-study of comparative genome analysis.

    Science.gov (United States)

    Zakham, F; Belayachi, L; Ussery, D; Akrim, M; Benjouad, A; El Aouad, R; Ennaji, M M

    2011-02-08

    The genus Mycobacterium represents more than 120 species including important pathogens of human and cause major public health problems and illnesses. Further, with more than 100 genome sequences from this genus, comparative genome analysis can provide new insights for better understanding the evolutionary events of these species and improving drugs, vaccines, and diagnostics tools for controlling Mycobacterial diseases. In this present study we aim to outline a comparative genome analysis of fourteen Mycobacterial genomes: M. avium subsp. paratuberculosis K—10, M. bovis AF2122/97, M. bovis BCG str. Pasteur 1173P2, M. leprae Br4923, M. marinum M, M. sp. KMS, M. sp. MCS, M. tuberculosis CDC1551, M. tuberculosis F11, M. tuberculosis H37Ra, M. tuberculosis H37Rv, M. tuberculosis KZN 1435 , M. ulcerans Agy99,and M. vanbaalenii PYR—1, For this purpose a comparison has been done based on their length of genomes, GC content, number of genes in different data bases (Genbank, Refseq, and Prodigal). The BLAST matrix of these genomes has been figured to give a lot of information about the similarity between species in a simple scheme. As a result of multiple genome analysis, the pan and core genome have been defined for twelve Mycobacterial species. We have also introduced the genome atlas of the reference strain M. tuberculosis H37Rv which can give a good overview of this genome. And for examining the phylogenetic relationships among these bacteria, a phylogenic tree has been constructed from 16S rRNA gene for tuberculosis and non tuberculosis Mycobacteria to understand the evolutionary events of these species.

  7. Progresses in studies of nuclear actin

    Institute of Scientific and Technical Information of China (English)

    ZHU Xiaojuan; ZENG Xianlu; SONG Zhaoxia; HAO Shui

    2004-01-01

    Actin is a protein abundant in cells. Recently, it has been proved to be universally existent in the nuclei of many cell types. Actin and actin-binding proteins, as well as actin-related proteins, are necessary for the mediation of the conformation and function of nuclear actin, including the transformation of actin between unpolymerized and polymerized, chroinatin remodeling, regulation of gene expression and RNA processing as well as RNA transportation. In this paper, we summarized the progresses in the research of nu clear actin.

  8. Genome-wide alterations of the DNA replication program during tumor progression

    Science.gov (United States)

    Arneodo, A.; Goldar, A.; Argoul, F.; Hyrien, O.; Audit, B.

    2016-08-01

    Oncogenic stress is a major driving force in the early stages of cancer development. Recent experimental findings reveal that, in precancerous lesions and cancers, activated oncogenes may induce stalling and dissociation of DNA replication forks resulting in DNA damage. Replication timing is emerging as an important epigenetic feature that recapitulates several genomic, epigenetic and functional specificities of even closely related cell types. There is increasing evidence that chromosome rearrangements, the hallmark of many cancer genomes, are intimately associated with the DNA replication program and that epigenetic replication timing changes often precede chromosomic rearrangements. The recent development of a novel methodology to map replication fork polarity using deep sequencing of Okazaki fragments has provided new and complementary genome-wide replication profiling data. We review the results of a wavelet-based multi-scale analysis of genomic and epigenetic data including replication profiles along human chromosomes. These results provide new insight into the spatio-temporal replication program and its dynamics during differentiation. Here our goal is to bring to cancer research, the experimental protocols and computational methodologies for replication program profiling, and also the modeling of the spatio-temporal replication program. To illustrate our purpose, we report very preliminary results obtained for the chronic myelogeneous leukemia, the archetype model of cancer. Finally, we discuss promising perspectives on using genome-wide DNA replication profiling as a novel efficient tool for cancer diagnosis, prognosis and personalized treatment.

  9. Whole genome comparative studies between chicken and turkey and their implications for avian genome evolution

    Directory of Open Access Journals (Sweden)

    Carré Wilfrid

    2008-04-01

    Full Text Available Abstract Background Comparative genomics is a powerful means of establishing inter-specific relationships between gene function/location and allows insight into genomic rearrangements, conservation and evolutionary phylogeny. The availability of the complete sequence of the chicken genome has initiated the development of detailed genomic information in other birds including turkey, an agriculturally important species where mapping has hitherto focused on linkage with limited physical information. No molecular study has yet examined conservation of avian microchromosomes, nor differences in copy number variants (CNVs between birds. Results We present a detailed comparative cytogenetic map between chicken and turkey based on reciprocal chromosome painting and mapping of 338 chicken BACs to turkey metaphases. Two inter-chromosomal changes (both involving centromeres and three pericentric inversions have been identified between chicken and turkey; and array CGH identified 16 inter-specific CNVs. Conclusion This is the first study to combine the modalities of zoo-FISH and array CGH between different avian species. The first insight into the conservation of microchromosomes, the first comparative cytogenetic map of any bird and the first appraisal of CNVs between birds is provided. Results suggest that avian genomes have remained relatively stable during evolution compared to mammalian equivalents.

  10. Genome-wide association study of multiplex schizophrenia pedigrees

    DEFF Research Database (Denmark)

    Levinson, Douglas F; Shi, Jianxin; Wang, Kai

    2012-01-01

    The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs).......The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs)....

  11. Teacher Stance in Creative Learning: A Study of Progression

    Science.gov (United States)

    Craft, Anna; Cremin, Teresa; Burnard, Pamela; Chappell, Kerry

    2007-01-01

    This paper reports focused findings from a qualitative scoping study undertaken in four sites in England focusing on progression in creative learning (PICL) (February 2005-January 2006), funded by Creative Partnerships, a national development programme. The study sought to explore how progression in creative learning can be described in two…

  12. An Integrative Breakage Model of genome architecture, reshuffling and evolution: The Integrative Breakage Model of genome evolution, a novel multidisciplinary hypothesis for the study of genome plasticity.

    Science.gov (United States)

    Farré, Marta; Robinson, Terence J; Ruiz-Herrera, Aurora

    2015-05-01

    Our understanding of genomic reorganization, the mechanics of genomic transmission to offspring during germ line formation, and how these structural changes contribute to the speciation process, and genetic disease is far from complete. Earlier attempts to understand the mechanism(s) and constraints that govern genome remodeling suffered from being too narrowly focused, and failed to provide a unified and encompassing view of how genomes are organized and regulated inside cells. Here, we propose a new multidisciplinary Integrative Breakage Model for the study of genome evolution. The analysis of the high-level structural organization of genomes (nucleome), together with the functional constrains that accompany genome reshuffling, provide insights into the origin and plasticity of genome organization that may assist with the detection and isolation of therapeutic targets for the treatment of complex human disorders. © 2015 WILEY Periodicals, Inc.

  13. CRISPR/Cas9 for genome editing: progress, implications and challenges.

    Science.gov (United States)

    Zhang, Feng; Wen, Yan; Guo, Xiong

    2014-09-15

    Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) protein 9 system provides a robust and multiplexable genome editing tool, enabling researchers to precisely manipulate specific genomic elements, and facilitating the elucidation of target gene function in biology and diseases. CRISPR/Cas9 comprises of a nonspecific Cas9 nuclease and a set of programmable sequence-specific CRISPR RNA (crRNA), which can guide Cas9 to cleave DNA and generate double-strand breaks at target sites. Subsequent cellular DNA repair process leads to desired insertions, deletions or substitutions at target sites. The specificity of CRISPR/Cas9-mediated DNA cleavage requires target sequences matching crRNA and a protospacer adjacent motif locating at downstream of target sequences. Here, we review the molecular mechanism, applications and challenges of CRISPR/Cas9-mediated genome editing and clinical therapeutic potential of CRISPR/Cas9 in future.

  14. Co-expression module analysis reveals biological processes, genomic gain, and regulatory mechanisms associated with breast cancer progression

    Directory of Open Access Journals (Sweden)

    Derow Catherine K

    2010-05-01

    Full Text Available Abstract Background Gene expression signatures are typically identified by correlating gene expression patterns to a disease phenotype of interest. However, individual gene-based signatures usually suffer from low reproducibility and interpretability. Results We have developed a novel algorithm Iterative Clique Enumeration (ICE for identifying relatively independent maximal cliques as co-expression modules and a module-based approach to the analysis of gene expression data. Applying this approach on a public breast cancer dataset identified 19 modules whose expression levels were significantly correlated with tumor grade. The correlations were reproducible for 17 modules in an independent breast cancer dataset, and the reproducibility was considerably higher than that based on individual genes or modules identified by other algorithms. Sixteen out of the 17 modules showed significant enrichment in certain Gene Ontology (GO categories. Specifically, modules related to cell proliferation and immune response were up-regulated in high-grade tumors while those related to cell adhesion was down-regulated. Further analyses showed that transcription factors NYFB, E2F1/E2F3, NRF1, and ELK1 were responsible for the up-regulation of the cell proliferation modules. IRF family and ETS family proteins were responsible for the up-regulation of the immune response modules. Moreover, inhibition of the PPARA signaling pathway may also play an important role in tumor progression. The module without GO enrichment was found to be associated with a potential genomic gain in 8q21-23 in high-grade tumors. The 17-module signature of breast tumor progression clustered patients into subgroups with significantly different relapse-free survival times. Namely, patients with lower cell proliferation and higher cell adhesion levels had significantly lower risk of recurrence, both for all patients (p = 0.004 and for those with grade 2 tumors (p = 0.017. Conclusions The ICE

  15. Construction of a genome-wide human BAC-Unigene resource. Final progress report, 1989--1996

    Energy Technology Data Exchange (ETDEWEB)

    Lim, C.S.; Xu, R.X.; Wang, M. [and others

    1996-12-31

    Currently, over 30,000 mapped STSs and 27,000 mapped Unigenes (non-redundant, unigene sets of cDNA representing EST clusters) are available for human alone. A total of 44,000 Unigene cDNA clones have been supplied by Research Genetics. Unigenes, or cDNAs are excellent resource for map building for two reasons. Firstly, they exist in two alternative forms -- as both sequence information for PCR primer pairs, and cDNA clones -- thus making library screening by colony hybridization as well as pooled library PCR possible. The authors have developed an efficient and robust procedure to screen genomic libraries with large number of DNA probes. Secondly, the linkage and order of expressed sequences, or genes are highly conserved among human, mouse and other mammalian species. Therefore, mapping with cDNA markers rather than random anonymous STSs will greatly facilitate comparative, evolutionary studies as well as physical map building. They have currently deconvoluted over 10,000 Unigene probes against a 4X coverage human BAC clones from the approved library D by high density colony hybridization method. 10,000 batches of Unigenes are arrayed in an imaginary 100 X 100 matrix from which 100 row pools and 100 column pools are obtained. Library filters are hybridized with pooled probes, thus reducing the number of hybridization required for addressing the positives for each Unigene from 10,000 to 200. Details on the experimental scheme as well as daily progress report is posted on the Web site (http://www.tree.caltech.edu).

  16. Study progresses on continuous curvilinear capsulorhexis

    Directory of Open Access Journals (Sweden)

    Bo Gao

    2015-10-01

    Full Text Available As the progress of modern techniques for cataract extraction surgery and various needs of intraocular lens(IOLimplantation, continuous curvilinear capsulorhexis(CCCis still in absolute dominance among different ways of incision of anterior capsular lens in clinical practices, due to its advantages such as smoothness of capsulor opening, strong anti-tearing ability, integrity of supporting capsular bag, and strength at maintaining IOL stability. This article describes in general the historical development of CCC and complementary methods adapted to raise success rate when it is used in special cases of cataract extraction surgery. Meanwhile, the article also discusses briefly and envisions the prospects of femotsecond laser applied in CCC technique for cataract extraction.

  17. A process for analysis of microarray comparative genomics hybridisation studies for bacterial genomes

    Directory of Open Access Journals (Sweden)

    Woodward Martin J

    2008-01-01

    Full Text Available Abstract Background Microarray based comparative genomic hybridisation (CGH experiments have been used to study numerous biological problems including understanding genome plasticity in pathogenic bacteria. Typically such experiments produce large data sets that are difficult for biologists to handle. Although there are some programmes available for interpretation of bacterial transcriptomics data and CGH microarray data for looking at genetic stability in oncogenes, there are none specifically to understand the mosaic nature of bacterial genomes. Consequently a bottle neck still persists in accurate processing and mathematical analysis of these data. To address this shortfall we have produced a simple and robust CGH microarray data analysis process that may be automated in the future to understand bacterial genomic diversity. Results The process involves five steps: cleaning, normalisation, estimating gene presence and absence or divergence, validation, and analysis of data from test against three reference strains simultaneously. Each stage of the process is described and we have compared a number of methods available for characterising bacterial genomic diversity, for calculating the cut-off between gene presence and absence or divergence, and shown that a simple dynamic approach using a kernel density estimator performed better than both established, as well as a more sophisticated mixture modelling technique. We have also shown that current methods commonly used for CGH microarray analysis in tumour and cancer cell lines are not appropriate for analysing our data. Conclusion After carrying out the analysis and validation for three sequenced Escherichia coli strains, CGH microarray data from 19 E. coli O157 pathogenic test strains were used to demonstrate the benefits of applying this simple and robust process to CGH microarray studies using bacterial genomes.

  18. Effectiveness study of atropine for progressive myopia in Europeans

    NARCIS (Netherlands)

    Polling, J.R.; Kok, R.G.; Tideman, J.W.; Meskat, B.; Klaver, C.C.W.

    2016-01-01

    PurposeRandomized controlled trials have shown the efficacy of atropine for progressive myopia, and this treatment has become the preferred pattern for this condition in Taiwan. This study explores the effectiveness of atropine 0.5% treatment for progressive high myopia and adherence to therapy in a

  19. Kodiak Island bald eagle migration and movements study: Progress report

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The purpose of this report is to update the progress of the bald eagle migration and movements study begun during July 1982. The study was initiated to: (1)...

  20. Integrated genome based studies of Shewanella ecophysiology

    Energy Technology Data Exchange (ETDEWEB)

    Saffarini, Daad A

    2013-03-07

    Progress is reported in these areas: Regulation of anaerobic respiration by cAMP receptor protein and role of adenylate cyclases; Identification of an octaheme c cytochrome as the terminal sulfite reductase in S. oneidensis MR-1; Identification and analysis of components of the electron transport chains that lead to reduction of thiosulfate, tetrathionate, and elemental sulfur in MR-1; Involvement of pili and flagella in metal reduction by S. oneidensis MR-1; and work suggesting that HemN1 is the major enzyme that is involved in heme biosynthesis under anaerobic conditions.

  1. Using functional genomics to study PINK1 and metabolic physiology

    DEFF Research Database (Denmark)

    Scheele, Camilla; Larsson, Ola; Timmons, James A

    2009-01-01

    in mammalian cells. Use of such technologies, inspired by nature's endogenous RNAi mechanism-microRNA targeting, comes with significant caveats. While the discipline of Pharmacology taught us last century that inhibitor action specificity is dependent on the concentration used, these experiences have been......Genome sequencing projects have provided the substrate for an unimaginable number of biological experiments. Further, genomic technologies such as microarrays and quantitative and exquisitely sensitive techniques such as real-time quantitative polymerase chain reaction have made it possible...... or experimental control. Thus, functional genomics is now being applied to study metabolic physiology with varying degrees of success. From the genome sequencing projects we also have the information needed to design chemical tools that can knock down a gene transcript, even distinguishing between splice variants...

  2. A Contrastive Study of Progressive Aspect in English and Chinese

    Institute of Scientific and Technical Information of China (English)

    田中锋

    2015-01-01

    Aspect, which is different from tense, deals with the internal structure of an action and allows people to describe or understand how an event unfolds over time. This paper examines the similarities and differences between English and Chinese progressive aspect in terms of form, meaning and use. The main findings are that in the first place the progressive aspect in both English and Chinese expresses the same core meaning, which is to describe the incomplete or ongoing state of an event or action. Secondly, the progressive aspect in English must be realized by grammatical device with inflectional changes, whereas in Chinese, it can be realized without verbal inflections (only with aspect markers). Thirdly, there exist differences between the English and Chinese progressive aspect in some specific usages. This contrastive study aims to deepen the understanding of the two languages, and provide practical and effective pedagogical suggestions for Chinese learners of English studying the progressive aspect.

  3. [Progress of genome engineering technology via clustered regularly interspaced short palindromic repeats--a review].

    Science.gov (United States)

    Li, Hao; Qiu, Shaofu; Song, Hongbin

    2013-10-04

    In survival competition with phage, bacteria and archaea gradually evolved the acquired immune system--Clustered regularly interspaced short palindromic repeats (CRISPR), presenting the trait of transcribing the crRNA and the CRISPR-associated protein (Cas) to silence or cleaving the foreign double-stranded DNA specifically. In recent years, strong interest arises in prokaryotes primitive immune system and many in-depth researches are going on. Recently, researchers successfully repurposed CRISPR as an RNA-guided platform for sequence-specific gene expression, which provides a simple approach for selectively perturbing gene expression on a genome-wide scale. It will undoubtedly bring genome engineering into a more convenient and accurate new era.

  4. Genomic Diversity and the Microenvironment as Drivers of Progression in DCIS

    Science.gov (United States)

    2015-10-01

    microenvironment, mammographic biomarkers 3. ACCOMPLISHMENTS What were the major goals of the project? Aim 1. Determine whether genetic diversity...of genetic diversity, microenvironmental diversity, and/or mammographic biomarkers can be used to predict which DCIS tumors are most likely to...series of pilot experiments to determine the best resource (Washington University) that we will use to perform the genomic sequencing of our tumors. We

  5. Potential assessment of genome-wide association study and genomic selection in Japanese pear Pyrus pyrifolia.

    Science.gov (United States)

    Iwata, Hiroyoshi; Hayashi, Takeshi; Terakami, Shingo; Takada, Norio; Sawamura, Yutaka; Yamamoto, Toshiya

    2013-03-01

    Although the potential of marker-assisted selection (MAS) in fruit tree breeding has been reported, bi-parental QTL mapping before MAS has hindered the introduction of MAS to fruit tree breeding programs. Genome-wide association studies (GWAS) are an alternative to bi-parental QTL mapping in long-lived perennials. Selection based on genomic predictions of breeding values (genomic selection: GS) is another alternative for MAS. This study examined the potential of GWAS and GS in pear breeding with 76 Japanese pear cultivars to detect significant associations of 162 markers with nine agronomic traits. We applied multilocus Bayesian models accounting for ordinal categorical phenotypes for GWAS and GS model training. Significant associations were detected at harvest time, black spot resistance and the number of spurs and two of the associations were closely linked to known loci. Genome-wide predictions for GS were accurate at the highest level (0.75) in harvest time, at medium levels (0.38-0.61) in resistance to black spot, firmness of flesh, fruit shape in longitudinal section, fruit size, acid content and number of spurs and at low levels (pear.

  6. Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression

    Directory of Open Access Journals (Sweden)

    Triche Timothy

    2009-12-01

    Full Text Available Abstract Background Pulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Results Using parallel oligonucleotide array platforms, shared orthologues between species were identified and normalized. The osteosarcoma expression signatures could not distinguish the canine and human diseases by hierarchical clustering. Cross-species target mining identified two genes, interleukin-8 (IL-8 and solute carrier family 1 (glial high affinity glutamate transporter, member 3 (SLC1A3, which were uniformly expressed in dog but not in all pediatric osteosarcoma patient samples. Expression of these genes in an independent population of pediatric osteosarcoma patients was associated with poor outcome (p = 0.020 and p = 0.026, respectively. Validation of IL-8 and SLC1A3 protein expression in pediatric osteosarcoma tissues further supported the potential value of these novel targets. Ongoing evaluation will validate the biological significance of these targets and their associated pathways. Conclusions Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapies.

  7. Proteomic and genomic studies of non-alcoholic fatty liver disease--clues in the pathogenesis.

    Science.gov (United States)

    Lim, Jun Wei; Dillon, John; Miller, Michael

    2014-07-14

    Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder that covers wide spectrum of liver pathology. NAFLD is strongly associated with liver inflammation, metabolic hyperlipidaemia and insulin resistance. Frequently, NAFLD has been considered as the hepatic manifestation of metabolic syndrome. The pathophysiology of NAFLD has not been fully elucidated. Some patients can remain in the stage of simple steatosis, which generally is a benign condition; whereas others can develop liver inflammation and progress into non-alcoholic steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. The mechanism behind the progression is still not fully understood. Much ongoing proteomic researches have focused on discovering the unbiased circulating biochemical markers to allow early detection and treatment of NAFLD. Comprehensive genomic studies have also begun to provide new insights into the gene polymorphism to understand patient-disease variations. Therefore, NAFLD is considered a complex and mutifactorial disease phenotype resulting from environmental exposures acting on a susceptible polygenic background. This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis. For proteomics section, this review highlighted functional proteins that involved in: (1) transportation; (2) metabolic pathway; (3) acute phase reaction; (4) anti-inflammatory; (5) extracellular matrix; and (6) immune system. In the genomic studies, this review will discuss genes which involved in: (1) lipolysis; (2) adipokines; and (3) cytokines production.

  8. Case Study Evaluations: A Decade of Progress?

    Science.gov (United States)

    Yin, Robert K.

    1997-01-01

    In the last 10 years, there has been increased use of case study methodology, with accompanying refinement and improvement of the methods. Case studies have become legitimate research methods in evaluation, but it is too soon to say whether improvements in methodology are really resulting in improvements in the case studies conducted. (SLD)

  9. Case Study Evaluations: A Decade of Progress?

    Science.gov (United States)

    Yin, Robert K.

    1997-01-01

    In the last 10 years, there has been increased use of case study methodology, with accompanying refinement and improvement of the methods. Case studies have become legitimate research methods in evaluation, but it is too soon to say whether improvements in methodology are really resulting in improvements in the case studies conducted. (SLD)

  10. Power analysis for genome-wide association studies

    Directory of Open Access Journals (Sweden)

    Klein Robert J

    2007-08-01

    Full Text Available Abstract Background Genome-wide association studies are a promising new tool for deciphering the genetics of complex diseases. To choose the proper sample size and genotyping platform for such studies, power calculations that take into account genetic model, tag SNP selection, and the population of interest are required. Results The power of genome-wide association studies can be computed using a set of tag SNPs and a large number of genotyped SNPs in a representative population, such as available through the HapMap project. As expected, power increases with increasing sample size and effect size. Power also depends on the tag SNPs selected. In some cases, more power is obtained by genotyping more individuals at fewer SNPs than fewer individuals at more SNPs. Conclusion Genome-wide association studies should be designed thoughtfully, with the choice of genotyping platform and sample size being determined from careful power calculations.

  11. Genomic Diversity and the Microenvironment as Drivers of Progression in DCIS

    Science.gov (United States)

    2016-10-01

    communication. This multi-disciplinary progress puts our group into an ideal position to fully implement the aims of the project and reach our year 3 and 4...were upstaged to invasive disease at definitive surgery. The other half of 99 testing subjects have been set aside for aim 3b work. For the first

  12. Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression.

    Science.gov (United States)

    Turner, Kristen M; Sun, Youting; Ji, Ping; Granberg, Kirsi J; Bernard, Brady; Hu, Limei; Cogdell, David E; Zhou, Xinhui; Yli-Harja, Olli; Nykter, Matti; Shmulevich, Ilya; Yung, W K Alfred; Fuller, Gregory N; Zhang, Wei

    2015-03-17

    Akt is a robust oncogene that plays key roles in the development and progression of many cancers, including glioma. We evaluated the differential propensities of the Akt isoforms toward progression in the well-characterized RCAS/Ntv-a mouse model of PDGFB-driven low grade glioma. A constitutively active myristoylated form of Akt1 did not induce high-grade glioma (HGG). In stark contrast, Akt2 and Akt3 showed strong progression potential with 78% and 97% of tumors diagnosed as HGG, respectively. We further revealed that significant variations in polarity and hydropathy values among the Akt isoforms in both the pleckstrin homology domain (P domain) and regulatory domain (R domain) were critical in mediating glioma progression. Gene expression profiles from representative Akt-derived tumors indicated dominant and distinct roles for Akt3, consisting primarily of DNA repair pathways. TCGA data from human GBM closely reflected the DNA repair function, as Akt3 was significantly correlated with a 76-gene signature DNA repair panel. Consistently, compared with Akt1 and Akt2 overexpression models, Akt3-expressing human GBM cells had enhanced activation of DNA repair proteins, leading to increased DNA repair and subsequent resistance to radiation and temozolomide. Given the wide range of Akt3-amplified cancers, Akt3 may represent a key resistance factor.

  13. Accounting for ancestry: population substructure and genome-wide association studies.

    Science.gov (United States)

    Tian, Chao; Gregersen, Peter K; Seldin, Michael F

    2008-10-15

    Accounting for the genetic substructure of human populations has become a major practical issue for studying complex genetic disorders. Allele frequency differences among ethnic groups and subgroups and admixture between different ethnic groups can result in frequent false-positive results or reduced power in genetic studies. Here, we review the problems and progress in defining population differences and the application of statistical methods to improve association studies. It is now possible to take into account the confounding effects of population stratification using thousands of unselected genome-wide single-nucleotide polymorphisms or, alternatively, selected panels of ancestry informative markers. These methods do not require any demographic information and therefore can be widely applied to genotypes available from multiple sources. We further suggest that it will be important to explore results in homogeneous population subsets as we seek to define the extent to which genomic variation influences complex phenotypes.

  14. Studies in genetic discrimination. Final progress report

    Energy Technology Data Exchange (ETDEWEB)

    1994-06-01

    We have screened 1006 respondents in a study of genetic discrimination. Analysis of these responses has produced evidence of the range of institutions engaged in genetic discrimination and demonstrates the impact of this discrimination on the respondents to the study. We have found that both ignorance and policy underlie genetic discrimination and that anti-discrimination laws are being violated.

  15. The Human Genome Project and Mental Retardation: An Educational Program. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Davis, Sharon

    1999-05-03

    The Arc, a national organization on mental retardation, conducted an educational program for members, many of whom have a family member with a genetic condition causing mental retardation. The project informed members about the Human Genome scientific efforts, conducted training regarding ethical, legal and social implications and involved members in issue discussions. Short reports and fact sheets on genetic and ELSI topics were disseminated to 2,200 of the Arc's leaders across the country and to other interested individuals. Materials produced by the project can e found on the Arc's web site, TheArc.org.

  16. Genome-wide Studies of Mycolic Acid Bacteria: Computational Identification and Analysis of a Minimal Genome

    KAUST Repository

    Kamanu, Frederick Kinyua

    2012-12-01

    The mycolic acid bacteria are a distinct suprageneric group of asporogenous Grampositive, high GC-content bacteria, distinguished by the presence of mycolic acids in their cell envelope. They exhibit great diversity in their cell and morphology; although primarily non-pathogens, this group contains three major pathogens Mycobacterium leprae, Mycobacterium tuberculosis complex, and Corynebacterium diphtheria. Although the mycolic acid bacteria are a clearly defined group of bacteria, the taxonomic relationships between its constituent genera and species are less well defined. Two approaches were tested for their suitability in describing the taxonomy of the group. First, a Multilocus Sequence Typing (MLST) experiment was assessed and found to be superior to monophyletic (16S small ribosomal subunit) in delineating a total of 52 mycolic acid bacterial species. Phylogenetic inference was performed using the neighbor-joining method. To further refine phylogenetic analysis and to take advantage of the widespread availability of bacterial genome data, a computational framework that simulates DNA-DNA hybridisation was developed and validated using multiscale bootstrap resampling. The tool classifies microbial genomes based on whole genome DNA, and was deployed as a web-application using PHP and Javascript. It is accessible online at http://cbrc.kaust.edu.sa/dna_hybridization/ A third study was a computational and statistical methods in the identification and analysis of a putative minimal mycolic acid bacterial genome so as to better understand (1) the genomic requirements to encode a mycolic acid bacterial cell and (2) the role and type of genes and genetic elements that lead to the massive increase in genome size in environmental mycolic acid bacteria. Using a reciprocal comparison approach, a total of 690 orthologous gene clusters forming a putative minimal genome were identified across 24 mycolic acid bacterial species. In order to identify new potential drug

  17. BACs as tools for the study of genomic imprinting.

    Science.gov (United States)

    Tunster, S J; Van De Pette, M; John, R M

    2011-01-01

    Genomic imprinting in mammals results in the expression of genes from only one parental allele. Imprinting occurs as a consequence of epigenetic marks set down either in the father's or the mother's germ line and affects a very specific category of mammalian gene. A greater understanding of this distinctive phenomenon can be gained from studies using large genomic clones, called bacterial artificial chromosomes (BACs). Here, we review the important applications of BACs to imprinting research, covering physical mapping studies and the use of BACs as transgenes in mice to study gene expression patterns, to identify imprinting centres, and to isolate the consequences of altered gene dosage. We also highlight the significant and unique advantages that rapid BAC engineering brings to genomic imprinting research.

  18. BACs as Tools for the Study of Genomic Imprinting

    Directory of Open Access Journals (Sweden)

    S. J. Tunster

    2011-01-01

    Full Text Available Genomic imprinting in mammals results in the expression of genes from only one parental allele. Imprinting occurs as a consequence of epigenetic marks set down either in the father's or the mother's germ line and affects a very specific category of mammalian gene. A greater understanding of this distinctive phenomenon can be gained from studies using large genomic clones, called bacterial artificial chromosomes (BACs. Here, we review the important applications of BACs to imprinting research, covering physical mapping studies and the use of BACs as transgenes in mice to study gene expression patterns, to identify imprinting centres, and to isolate the consequences of altered gene dosage. We also highlight the significant and unique advantages that rapid BAC engineering brings to genomic imprinting research.

  19. Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity.

    Directory of Open Access Journals (Sweden)

    Karin R McDonald

    2016-09-01

    Full Text Available Replicative DNA helicases expose the two strands of the double helix to the replication apparatus, but accessory helicases are often needed to help forks move past naturally occurring hard-to-replicate sites, such as tightly bound proteins, RNA/DNA hybrids, and DNA secondary structures. Although the Schizosaccharomyces pombe 5'-to-3' DNA helicase Pfh1 is known to promote fork progression, its genomic targets, dynamics, and mechanisms of action are largely unknown. Here we address these questions by integrating genome-wide identification of Pfh1 binding sites, comprehensive analysis of the effects of Pfh1 depletion on replication and DNA damage, and proteomic analysis of Pfh1 interaction partners by immunoaffinity purification mass spectrometry. Of the 621 high confidence Pfh1-binding sites in wild type cells, about 40% were sites of fork slowing (as marked by high DNA polymerase occupancy and/or DNA damage (as marked by high levels of phosphorylated H2A. The replication and integrity of tRNA and 5S rRNA genes, highly transcribed RNA polymerase II genes, and nucleosome depleted regions were particularly Pfh1-dependent. The association of Pfh1 with genomic integrity at highly transcribed genes was S phase dependent, and thus unlikely to be an artifact of high transcription rates. Although Pfh1 affected replication and suppressed DNA damage at discrete sites throughout the genome, Pfh1 and the replicative DNA polymerase bound to similar extents to both Pfh1-dependent and independent sites, suggesting that Pfh1 is proximal to the replication machinery during S phase. Consistent with this interpretation, Pfh1 co-purified with many key replisome components, including the hexameric MCM helicase, replicative DNA polymerases, RPA, and the processivity clamp PCNA in an S phase dependent manner. Thus, we conclude that Pfh1 is an accessory DNA helicase that interacts with the replisome and promotes replication and suppresses DNA damage at hard

  20. Progress of Gas Hydrate Studies in China

    Institute of Scientific and Technical Information of China (English)

    樊栓狮; 汪集旸

    2006-01-01

    A brief overview is given on the gas hydrate-related research activities carried out by Chinese researchers in the past 15 years. The content involves: (1) Historical review. Introducing the gas hydrate research history in China; (2) Gas hydrate research groups in China. There are nearly 20 groups engaged in gas hydrate research now; (3) Present studies.Including fundamental studies, status of the exploration of natural gas hydrate resources in the South China Sea region, and development of hydrate-based new techniques; (4) Future development.

  1. Genomic changes defining the progression of human colorectal and cervical tumors

    OpenAIRE

    1996-01-01

    Defining changes during the carcinogenesis and progression of tumors is a major way to obtain a better understanding of the mechanisms of cancer development. We therefore investigated the cacinogenesis process in the colon-rectum and in the uterine cervix by different cellchemical, immunohistochemical and cytogenetic methods. Cell proliferation, assessed by immunohistochemical detection of the Ki-67 antigen (MIB 1 antibody), DNA ploify, determined by image cytometry, e...

  2. Studies on Moss Flora Make Progress

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ A research group led by Prof. Gao Qian (Chien Gao) from the CAS Shenyang Institute of Applied Ecology was recently awarded a first prize in natural science by Liaoning Province in recognition of its many years of bryophyte studies. The award was conferred by S&T authorities of the northeast China province.

  3. A genome-wide association study of anorexia nervosa

    NARCIS (Netherlands)

    Boraska, V; Franklin, C S; Floyd, J A B; Thornton, L M; Huckins, L M; Southam, L; Rayner, N W; Tachmazidou, I; Klump, K L; Treasure, J; Lewis, C M; Schmidt, U; Tozzi, F; Kiezebrink, K; Hebebrand, J; Gorwood, P; Adan, R A H; Kas, M J H; Favaro, A; Santonastaso, P; Fernández-Aranda, F; Gratacos, M; Rybakowski, F; Dmitrzak-Weglarz, M; Kaprio, J; Keski-Rahkonen, A; Raevuori, A; Van Furth, E F; Slof-Op 't Landt, M C T; Hudson, J I; Reichborn-Kjennerud, T; Knudsen, G P S; Monteleone, P; Kaplan, A S; Karwautz, A; Hakonarson, H; Berrettini, W H; Guo, Y; Li, D; Schork, N J; Komaki, G; Ando, T; Inoko, H; Esko, T; Fischer, K; Männik, K; Metspalu, A; Baker, J H; Cone, R D; Dackor, J; DeSocio, J E; Hilliard, C E; O'Toole, J K; Pantel, J; Szatkiewicz, J P; Taico, C; Zerwas, S; Trace, S E; Davis, O S P; Helder, S; Bühren, K; Burghardt, R; de Zwaan, M; Egberts, K; Ehrlich, S; Herpertz-Dahlmann, B; Herzog, W; Imgart, H; Scherag, A; Scherag, S; Zipfel, S; Boni, C; Ramoz, N; Versini, A; Brandys, M K; Danner, U N; de Kovel, C; Hendriks, J; Koeleman, B P C; Ophoff, R A; Strengman, E; van Elburg, Annemarie; Bruson, A; Clementi, M; Degortes, D; Forzan, M; Tenconi, E; Docampo, E; Escaramís, G; Jiménez-Murcia, S; Lissowska, J; Rajewski, A; Szeszenia-Dabrowska, N; Slopien, A; Hauser, J; Karhunen, L; Meulenbelt, I; Slagboom, P E; Tortorella, A; Maj, M; Dedoussis, G; Dikeos, D; Gonidakis, F; Tziouvas, K; Tsitsika, A; Papezova, H; Slachtova, L; Martaskova, D; Kennedy, J L; Levitan, R D; Yilmaz, Z; Huemer, J; Koubek, D; Merl, E; Wagner, G; Lichtenstein, P; Breen, G; Cohen-Woods, S; Farmer, A; McGuffin, P; Cichon, S; Giegling, I; Herms, S; Rujescu, D; Schreiber, S; Wichmann, H-E; Dina, C; Sladek, R; Gambaro, G; Soranzo, N; Julia, A; Marsal, S; Rabionet, R; Gaborieau, V; Dick, D M; Palotie, A; Ripatti, S; Widén, E; Andreassen, O A; Espeseth, T; Lundervold, A; Reinvang, I; Steen, V M; Le Hellard, S; Mattingsdal, M; Ntalla, I; Bencko, V; Foretova, L; Janout, V; Navratilova, M; Gallinger, S; Pinto, D; Scherer, S W; Aschauer, H; Carlberg, L; Schosser, A; Alfredsson, L; Ding, B; Klareskog, L; Padyukov, L; Courtet, P; Guillaume, S; Jaussent, I; Finan, C; Kalsi, G; Roberts, M; Logan, D W; Peltonen, L; Ritchie, G R S; Barrett, J C; Estivill, X; Hinney, A; Sullivan, P F; Collier, D A; Zeggini, E; Bulik, C M

    2014-01-01

    Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countri

  4. INTEGRATED GENOME-BASED STUDIES OF SHEWANELLA ECOPHYSIOLOGY

    Energy Technology Data Exchange (ETDEWEB)

    TIEDJE, JAMES M; KONSTANTINIDIS, KOSTAS; WORDEN, MARK

    2014-01-08

    The aim of the work reported is to study Shewanella population genomics, and to understand the evolution, ecophysiology, and speciation of Shewanella. The tasks supporting this aim are: to study genetic and ecophysiological bases defining the core and diversification of Shewanella species; to determine gene content patterns along redox gradients; and to Investigate the evolutionary processes, patterns and mechanisms of Shewanella.

  5. Advances in plant cell type-specific genome-wide studies of gene expression

    Institute of Scientific and Technical Information of China (English)

    Ying WANG; Yuling JIAO

    2011-01-01

    Cell is the functional unit of life.To study the complex interactions of systems of biological molecules,it is crucial to dissect these molecules at the cell level.In recent years,major progresses have been made by plant biologists to profile gene expression in specific cell types at the genome-wide level.Approaches based on the isolation of cells,polysomes or nuclei have been developed and successfully used for studying the cell types from distinct organs of several plant species.These cell-level data sets revealed previously unrecognized cellular properties,such as cell-specific gene expression modules and hormone response centers,and should serve as essential resources for functional genomic analyses.Newly developed technologies are more affordable to many laboratories and should help to provide new insights at the cellular resolution in the near future.

  6. Genome-wide association studies and resting heart rate

    DEFF Research Database (Denmark)

    Oskari Kilpeläinen, Tuomas

    2016-01-01

    Genome-wide association studies (GWASs) have revolutionized the search for genetic variants regulating resting heart rate. In the last 10 years, GWASs have led to the identification of at least 21 novel heart rate loci. These discoveries have provided valuable insights into the mechanisms...... and pathways that regulate heart rate and link heart rate to cardiovascular morbidity and mortality. GWASs capture majority of genetic variation in a population sample by utilizing high-throughput genotyping chips measuring genotypes for up to several millions of SNPs across the genome in thousands...... of individuals. This allows the identification of the strongest heart rate associated signals at genome-wide level. While GWASs provide robust statistical evidence of the association of a given genetic locus with heart rate, they are only the starting point for detailed follow-up studies to locate the causal...

  7. ICPP water inventory study progress report

    Energy Technology Data Exchange (ETDEWEB)

    Richards, B.T.

    1993-05-01

    Recent data from the Idaho Chemical Processing Plant (ICPP) indicate that water is entering the sumps located in the bottom of Tank Firm Vaults in quantities that exceed expected levels. In addition, perched water body(s) exist beneath the northern portion of the ICPP. Questions have been raised concerning the origin of water entering the Tank Farm sumps and the recharge sources for the perched water bodies. Therefore, in an effort to determine the source of water, a project has been initiated to identify the source of water for Tank Farm sumps and the perched water bodies. In addition, an accurate water balance for the ICPP will be developed. The purpose of this report is to present the specific results and conclusions for the ICPP water balance portion of the study. In addition, the status of the other activities being conducted as part of study, along with the associated action plans, is provided.

  8. Progress report on nuclear spectroscopic studies

    Energy Technology Data Exchange (ETDEWEB)

    Bingham, C.R.; Guidry, M.W.; Riedinger, L.L.; Sorensen, S.P.

    1994-02-18

    The Nuclear Physics group at the University of Tennessee, Knoxville (UTK) is involved in several aspects of heavy-ion physics including both nuclear structure and reaction mechanisms. While the main emphasis is on experimental problems, the authors have maintained a strong collaboration with several theorists in order to best pursue the physics of their measurements. During the last year they have had several experiments at the ATLAS at Argonne National Laboratory, the GAMMASPHERE at the LBL 88 Cyclotron, and with the NORDBALL at the Niels Bohr Institute Tandem. Also, they continue to be very active in the WA93/98 collaboration studying ultra-relativistic heavy ion physics utilizing the SPS accelerator at CERN in Geneva, Switzerland and in the PHENIX Collaboration at the RHIC accelerator under construction at Brookhaven National Laboratory. During the last year their experimental work has been in three broad areas: (1) the structure of nuclei at high angular momentum, (2) the structure of nuclei far from stability, and (3) ultra-relativistic heavy-ion physics. The results of studies in these particular areas are described in this document. These studies concentrate on the structure of nuclear matter in extreme conditions of rotational motion, imbalance of neutrons and protons, or very high temperature and density. Another area of research is heavy-ion-induced transfer reactions, which utilize the transfer of nucleons to states with high angular momentum to learn about their structure and to understand the transfer of particles, energy, and angular momentum in collisions between heavy ions.

  9. Improving livestock for agriculture - technological progress from random transgenesis to precision genome editing heralds a new era.

    Science.gov (United States)

    Laible, Götz; Wei, Jingwei; Wagner, Stefan

    2015-01-01

    Humans have a long history in shaping the genetic makeup of livestock to optimize production and meet growing human demands for food and other animal products. Until recently, this has only been possible through traditional breeding and selection, which is a painstakingly slow process of accumulating incremental gains over a long period. The development of transgenic livestock technology offers a more direct approach with the possibility for making genetic improvements with greater impact and within a single generation. However, initially the technology was hampered by technical difficulties and limitations, which have now largely been overcome by progressive improvements over the past 30 years. Particularly, the advent of genome editing in combination with homologous recombination has added a new level of efficiency and precision that holds much promise for the genetic improvement of livestock using the increasing knowledge of the phenotypic impact of genetic sequence variants. So far not a single line of transgenic livestock has gained approval for commercialization. The step change to genome-edited livestock with precise sequence changes may accelerate the path to market, provided applications of this new technology for agriculture can deliver, in addition to economic incentives for producers, also compelling benefits for animals, consumers, and the environment.

  10. Exploring relationships between host genome and microbiome: new insights from genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Muslihudeen Abdul-Razaq Abdul-Aziz

    2016-10-01

    Full Text Available As our understanding of the human microbiome expands, impacts on health and disease continue to be revealed. Alterations in the microbiome can result in dysbiosis, which has now been linked to subsequent autoimmune and metabolic diseases, highlighting the need to identify factors that shape the microbiome. Research has identified that the composition and functions of the human microbiome can be influenced by diet, age, gender, and environment. More recently, studies have explored how human genetic variation may also influence the microbiome. Here, we review several recent analytical advances in this new research area, including those that use genome-wide association studies to examine host genome-microbiome interactions, while controlling for the influence of other factors. We find that current research is limited by small sample sizes, lack of cohort replication, and insufficient confirmatory mechanistic studies. In addition, we discuss the importance of understanding long-term interactions between the host genome and microbiome, as well as the potential impacts of disrupting this relationship, and explore new research avenues that may provide information about the co-evolutionary history of humans and their microorganisms.

  11. Progress report on nuclear spectroscopic studies

    Energy Technology Data Exchange (ETDEWEB)

    Bingham, C.R.; Riedinger, L.L.; Sorensen, S.P.

    1996-01-16

    The experimental program in nuclear physics at the University of Tennessee, Knoxville, is led by Professors Carrol Bingham, Lee Riedinger, and Soren Sorenseni who respectively lead the studies of the exotic decay modes of nuclei far from stability, the program of high-spin research, and our effort in relativistic heavy-ion physics. Over the years, this broad program of research has been successful partially because of the shared University resources applied to this group effort. The proximity of the Oak Ridge National Laboratory has allowed us to build extremely strong programs of joint research, and in addition to play an important leadership role in the Joint Institute for Heavy Ion Research (JIHIR). Our experimental program is also very closely linked with those at other national laboratories: Argonne (collaborations involving the Fragment Mass Analyzer (FMA) and {gamma}-ray arrays), Brookhaven (the RHIC and Phenix projects), and Berkeley (GAMMASPHERE). We have worked closely with a variety of university groups in the last three years, especially those in the UNISOR and now UNIRIB collaborations. And, in all aspects of our program, we have maintained close collaborations with theorists, both to inspire the most exciting experiments to perform and to extract the pertinent physics from the results. The specific areas discussed in this report are: properties of high-spin states; study of low-energy levels of nuclei far from stability; and high energy heavy-ion physics.

  12. Progress in the study of tectophysicochemistry

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Tectophysicochemistry is a research area that deals with the interrelations between physical and chemical changes of crustal materials caused by tectonism. A given tectonic force may be resolved into two parts: homogeneous stress and differential stress. Homogeneous stress refers to isotopic pressure, which is superimposed on the original pressure and affects the equilibrium of various chemical reactions. It is also a factor that influences petrogenesis, metallogenesis and metamorphism. Differential stress is commonly produced when external forces act on a given solid body. It may cause deformation of crustal materials and generate various kinds of structural features. Tectophysicochemistry pays special attention to pressure, temperature and other physicochemical conditions produced or induced by tectonism and studies the influences of additional tectonic parameters on various chemical equilibria, so it gradually develops into an independent area of science.

  13. Studies in development immunogenetics. Annual progress report

    Energy Technology Data Exchange (ETDEWEB)

    Owen, R D

    1975-03-26

    This contract provides the research support for a group concerned with a relatively large range of problems. The integrating thread that runs through it is that of an interest in development and its genetic regulation, mainly in complex organisms and with an emphasis on the immune system as a model for developmental analysis and as a tool for following the development of other systems, especially the brain. It includes studies of biochemical genetics, primarily from a developmental viewpoint and with particular regard to defense mechanisms, and cellular aspects of the immune system. It extends into the area of cancer immunology and cell specificities as related to tumor systems, primarily from an immunogenetic viewpoint and with particular reference to leukemias in the mouse, and to disruptions of genetic control mechanisms in tumor development, especially as approached through the reappearance of fetal antigens associated with tumor development.

  14. Studies in developmental immunogenetics. Annual progress report

    Energy Technology Data Exchange (ETDEWEB)

    Owen, R D

    1977-06-29

    This contract provides the research support for a group concerned with a relatively large range of problems. The integrating thread that runs through it is that of an interest in development and its genetic regulation, mainly in complex organisms and with an emphasis on the immune system as a model for developmental analysis and as a tool for following the development of other systems, especially the brain. It includes studies of biochemical genetics, primarily from a developmental viewpoint and with particular regard to defense mechanisms, and cellular aspects of the immune system. It extends into the area of cancer immunology and cell specificities as related to tumor systems and to disruptions of genetic control mechanisms in tumor development, especially as approached through the reappearance of fetal antigens associated with tumor development. During the past year, our attention has turned increasingly to genetic factors predisposing to autoimmune disease, and to factors that have been claimed to transfer specific cellular immunity from immune to nonimmune animals.

  15. Combing genomic DNA for structural and functional studies.

    Science.gov (United States)

    Schurra, Catherine; Bensimon, Aaron

    2009-01-01

    Molecular combing is a process whereby single DNA molecules bind by their extremities to a silanised surface and are then uniformly stretched and aligned by a receding air/water interface (1). This method, with a high resolution ranging from a few kilobases to megabases, has many applications in the field of molecular cytogenetics, allowing structural and functional analysis at the genome level. Here we describe protocols for preparing DNA for combing and for the use of fluorescent hybridisation (FH) applied to combed DNA to conduct physical mapping or genomic structural analysis. We also present the methodology for visualising and studying DNA replication using combed DNA.

  16. Listeria Genomics

    Science.gov (United States)

    Cabanes, Didier; Sousa, Sandra; Cossart, Pascale

    The opportunistic intracellular foodborne pathogen Listeria monocytogenes has become a paradigm for the study of host-pathogen interactions and bacterial adaptation to mammalian hosts. Analysis of L. monocytogenes infection has provided considerable insight into how bacteria invade cells, move intracellularly, and disseminate in tissues, as well as tools to address fundamental processes in cell biology. Moreover, the vast amount of knowledge that has been gathered through in-depth comparative genomic analyses and in vivo studies makes L. monocytogenes one of the most well-studied bacterial pathogens. This chapter provides an overview of progress in the exploration of genomic, transcriptomic, and proteomic data in Listeria spp. to understand genome evolution and diversity, as well as physiological aspects of metabolism used by bacteria when growing in diverse environments, in particular in infected hosts.

  17. From genome to function by studying eQTLs

    NARCIS (Netherlands)

    Westra, Harm-Jan; Franke, Lude

    2014-01-01

    Genome-wide association studies (GWASs) have shown a large number of genetic variants to be associated with complex diseases. The identification of the causal variant within an associated locus can sometimes be difficult because of the linkage disequilibrium between the associated variants and becau

  18. Genome-wide association study identifies five new schizophrenia loci

    NARCIS (Netherlands)

    Ripke, Stephan; Sanders, Alan R.; Kendler, Kenneth S.; Levinson, Douglas F.; Sklar, Pamela; Holmans, Peter A.; Lin, Dan-Yu; Duan, Jubao; Ophoff, Roel A.; Andreassen, Ole A.; Scolnick, Edward; Cichon, Sven; Clair, David St.; Corvin, Aiden; Gurling, Hugh; Werge, Thomas; Rujescu, Dan; Blackwood, Douglas H. R.; Pato, Carlos N.; Malhotra, Anil K.; Purcell, Shaun; Dudbridge, Frank; Neale, Benjamin M.; Rossin, Lizzy; Visscher, Peter M.; Posthuma, Danielle; Ruderfer, Douglas M.; Fanous, Ayman; Stefansson, Hreinn; Steinberg, Stacy; Mowry, Bryan J.; Golimbet, Vera; De Hert, Marc; Jonsson, Erik G.; Bitter, Istvan; Pietilainen, Olli P. H.; Collier, David A.; Tosato, Sarah; Agartz, Ingrid; Albus, Margot; Alexander, Madeline; Amdur, Richard L.; Amin, Farooq; Bass, Nicholas; Bergen, Sarah E.; Black, Donald W.; Borglum, Anders D.; Brown, Matthew A.; Bruggeman, Richard; Buccola, Nancy G.; Byerley, William F.; Cahn, Wiepke; Cantor, Rita M.; Carr, Vaughan J.; Catts, Stanley V.; Choudhury, Khalid; Cloninger, C. Robert; Cormican, Paul; Craddock, Nicholas; Danoy, Patrick A.; Datta, Susmita; De Haan, Lieuwe; Demontis, Ditte; Dikeos, Dimitris; Djurovic, Srdjan; Donnelly, Peter; Donohoe, Gary; Duong, Linh; Dwyer, Sarah; Fink-Jensen, Anders; Freedman, Robert; Freimer, Nelson B.; Friedl, Marion; Georgieva, Lyudmila; Giegling, Ina; Gill, Michael; Glenthoj, Birte; Godard, Stephanie; Hamshere, Marian; Hansen, Mark; Hansen, Thomas; Hartmann, Annette M.; Henskens, Frans A.; Hougaard, David M.; Hultman, Christina M.; Ingason, Andres; Jablensky, Assen V.; Jakobsen, Klaus D.; Jay, Maurice; Juergens, Gesche; Kahn, Renes; Keller, Matthew C.; Kenis, Gunter; Kenny, Elaine; Kim, Yunjung; Kirov, George K.; Konnerth, Heike; Konte, Bettina; Krabbendam, Lydia; Krasucki, Robert; Lasseter, Virginia K.; Laurent, Claudine; Lawrence, Jacob; Lencz, Todd; Lerer, F. Bernard; Liang, Kung-Yee; Lichtenstein, Paul; Lieberman, Jeffrey A.; Linszen, Don H.; Lonnqvist, Jouko; Loughland, Carmel M.; Maclean, Alan W.; Maher, Brion S.; Maier, Wolfgang; Mallet, Jacques; Malloy, Pat; Mattheisen, Manuel; Mattingsdal, Morten; McGhee, Kevin A.; McGrath, John J.; McIntosh, Andrew; McLean, Duncan E.; McQuillin, Andrew; Melle, Ingrid; Michie, Patricia T.; Milanova, Vihra; Morris, Derek W.; Mors, Ole; Mortensen, Preben B.; Moskvina, Valentina; Muglia, Pierandrea; Myin-Germeys, Inez; Nertney, Deborah A.; Nestadt, Gerald; Nielsen, Jimmi; Nikolov, Ivan; Nordentoft, Merete; Norton, Nadine; Noethen, Markus M.; O'Dushlaine, Colm T.; Olincy, Ann; Olsen, Line; O'Neill, F. Anthony; Orntoft, Torben F.; Owen, Michael J.; Pantelis, Christos; Papadimitriou, George; Pato, Michele T.; Peltonen, Leena; Petursson, Hannes; Pickard, Ben; Pimm, Jonathan; Pulver, Ann E.; Puri, Vinay; Quested, Digby; Quinn, Emma M.; Rasmussen, Henrik B.; Rethelyi, Janos M.; Ribble, Robert; Rietschel, Marcella; Riley, Brien P.; Ruggeri, Mirella; Schall, Ulrich; Schulze, Thomas G.; Schwab, Sibylle G.; Scott, Rodney J.; Shi, Jianxin; Sigurdsson, Engilbert; Silverman, Jeremy M.; Spencer, Chris C. A.; Stefansson, Kari; Strange, Amy; Strengman, Eric; Stroup, T. Scott; Suvisaari, Jaana; Terenius, Lars; Thirumalai, Srinivasa; Thygesen, Johan H.; Timm, Sally; Toncheva, Draga; van den Oord, Edwin; van Os, Jim; van Winkel, Ruud; Veldink, Jan; Walsh, Dermot; Wang, August G.; Wiersma, Durk; Wildenauer, Dieter B.; Williams, Hywel J.; Williams, Nigel M.; Wormley, Brandon; Zammit, Stan; Sullivan, Patrick F.; O'Donovan, Michael C.; Daly, Mark J.; Gejman, Pablo V.

    2011-01-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded

  19. Genomic studies of mood disorders - the brain as a muscle?

    OpenAIRE

    Niculescu, Alexander B.

    2005-01-01

    Recent genomic studies showing abnormalities in the fibroblast growth factor system in the postmortem brains of people with major depressive disorder support previous indications of a role for growth factors in mood disorders. Similar molecular pathways, volumetric changes, and the effects of exercise on mood suggest a superficial analogy, and perhaps a deeper relationship, between muscle and brain functioning.

  20. Genome-wide association study identifies five new schizophrenia loci

    NARCIS (Netherlands)

    Ripke, Stephan; Sanders, Alan R.; Kendler, Kenneth S.; Levinson, Douglas F.; Sklar, Pamela; Holmans, Peter A.; Lin, Dan-Yu; Duan, Jubao; Ophoff, Roel A.; Andreassen, Ole A.; Scolnick, Edward; Cichon, Sven; Clair, David St.; Corvin, Aiden; Gurling, Hugh; Werge, Thomas; Rujescu, Dan; Blackwood, Douglas H. R.; Pato, Carlos N.; Malhotra, Anil K.; Purcell, Shaun; Dudbridge, Frank; Neale, Benjamin M.; Rossin, Lizzy; Visscher, Peter M.; Posthuma, Danielle; Ruderfer, Douglas M.; Fanous, Ayman; Stefansson, Hreinn; Steinberg, Stacy; Mowry, Bryan J.; Golimbet, Vera; De Hert, Marc; Jonsson, Erik G.; Bitter, Istvan; Pietilainen, Olli P. H.; Collier, David A.; Tosato, Sarah; Agartz, Ingrid; Albus, Margot; Alexander, Madeline; Amdur, Richard L.; Amin, Farooq; Bass, Nicholas; Bergen, Sarah E.; Black, Donald W.; Borglum, Anders D.; Brown, Matthew A.; Bruggeman, Richard; Buccola, Nancy G.; Byerley, William F.; Cahn, Wiepke; Cantor, Rita M.; Carr, Vaughan J.; Catts, Stanley V.; Choudhury, Khalid; Cloninger, C. Robert; Cormican, Paul; Craddock, Nicholas; Danoy, Patrick A.; Datta, Susmita; De Haan, Lieuwe; Demontis, Ditte; Dikeos, Dimitris; Djurovic, Srdjan; Donnelly, Peter; Donohoe, Gary; Duong, Linh; Dwyer, Sarah; Fink-Jensen, Anders; Freedman, Robert; Freimer, Nelson B.; Friedl, Marion; Georgieva, Lyudmila; Giegling, Ina; Gill, Michael; Glenthoj, Birte; Godard, Stephanie; Hamshere, Marian; Hansen, Mark; Hansen, Thomas; Hartmann, Annette M.; Henskens, Frans A.; Hougaard, David M.; Hultman, Christina M.; Ingason, Andres; Jablensky, Assen V.; Jakobsen, Klaus D.; Jay, Maurice; Juergens, Gesche; Kahn, Renes; Keller, Matthew C.; Kenis, Gunter; Kenny, Elaine; Kim, Yunjung; Kirov, George K.; Konnerth, Heike; Konte, Bettina; Krabbendam, Lydia; Krasucki, Robert; Lasseter, Virginia K.; Laurent, Claudine; Lawrence, Jacob; Lencz, Todd; Lerer, F. Bernard; Liang, Kung-Yee; Lichtenstein, Paul; Lieberman, Jeffrey A.; Linszen, Don H.; Lonnqvist, Jouko; Loughland, Carmel M.; Maclean, Alan W.; Maher, Brion S.; Maier, Wolfgang; Mallet, Jacques; Malloy, Pat; Mattheisen, Manuel; Mattingsdal, Morten; McGhee, Kevin A.; McGrath, John J.; McIntosh, Andrew; McLean, Duncan E.; McQuillin, Andrew; Melle, Ingrid; Michie, Patricia T.; Milanova, Vihra; Morris, Derek W.; Mors, Ole; Mortensen, Preben B.; Moskvina, Valentina; Muglia, Pierandrea; Myin-Germeys, Inez; Nertney, Deborah A.; Nestadt, Gerald; Nielsen, Jimmi; Nikolov, Ivan; Nordentoft, Merete; Norton, Nadine; Noethen, Markus M.; O'Dushlaine, Colm T.; Olincy, Ann; Olsen, Line; O'Neill, F. Anthony; Orntoft, Torben F.; Owen, Michael J.; Pantelis, Christos; Papadimitriou, George; Pato, Michele T.; Peltonen, Leena; Petursson, Hannes; Pickard, Ben; Pimm, Jonathan; Pulver, Ann E.; Puri, Vinay; Quested, Digby; Quinn, Emma M.; Rasmussen, Henrik B.; Rethelyi, Janos M.; Ribble, Robert; Rietschel, Marcella; Riley, Brien P.; Ruggeri, Mirella; Schall, Ulrich; Schulze, Thomas G.; Schwab, Sibylle G.; Scott, Rodney J.; Shi, Jianxin; Sigurdsson, Engilbert; Silverman, Jeremy M.; Spencer, Chris C. A.; Stefansson, Kari; Strange, Amy; Strengman, Eric; Stroup, T. Scott; Suvisaari, Jaana; Terenius, Lars; Thirumalai, Srinivasa; Thygesen, Johan H.; Timm, Sally; Toncheva, Draga; van den Oord, Edwin; van Os, Jim; van Winkel, Ruud; Veldink, Jan; Walsh, Dermot; Wang, August G.; Wiersma, Durk; Wildenauer, Dieter B.; Williams, Hywel J.; Williams, Nigel M.; Wormley, Brandon; Zammit, Stan; Sullivan, Patrick F.; O'Donovan, Michael C.; Daly, Mark J.; Gejman, Pablo V.

    2011-01-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded

  1. Genome-wide association study identifies five new schizophrenia loci

    DEFF Research Database (Denmark)

    Ripke, Stephan; Sanders, Alan R; Kendler, Kenneth S

    2011-01-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yiel...

  2. Genome-Wide Association Study of HIV Whole Genome Sequences Validated using Drug Resistance

    Science.gov (United States)

    Power, Robert A.; Davaniah, Siva; Derache, Anne; Wilkinson, Eduan; Tanser, Frank; Pillay, Deenan; de Oliveira, Tulio

    2016-01-01

    Background Genome-wide association studies (GWAS) have considerably advanced our understanding of human traits and diseases. With the increasing availability of whole genome sequences (WGS) for pathogens, it is important to establish whether GWAS of viral genomes could reveal important biological insights. Here we perform the first proof of concept viral GWAS examining drug resistance (DR), a phenotype with well understood genetics. Method We performed a GWAS of DR in a sample of 343 HIV subtype C patients failing 1st line antiretroviral treatment in rural KwaZulu-Natal, South Africa. The majority and minority variants within each sequence were called using PILON, and GWAS was performed within PLINK. HIV WGS from patients failing on different antiretroviral treatments were compared to sequences derived from individuals naïve to the respective treatment. Results GWAS methodology was validated by identifying five associations on a genetic level that led to amino acid changes known to cause DR. Further, we highlighted the ability of GWAS to identify epistatic effects, identifying two replicable variants within amino acid 68 of the reverse transcriptase protein previously described as potential fitness compensatory mutations. A possible additional DR variant within amino acid 91 of the matrix region of the Gag protein was associated with tenofovir failure, highlighting GWAS’s ability to identify variants outside classical candidate genes. Our results also suggest a polygenic component to DR. Conclusions These results validate the applicability of GWAS to HIV WGS data even in relative small samples, and emphasise how high throughput sequencing can provide novel and clinically relevant insights. Further they suggested that for viruses like HIV, population structure was only minor concern compared to that seen in bacteria or parasite GWAS. Given the small genome length and reduced burden for multiple testing, this makes HIV an ideal candidate for GWAS. PMID:27677172

  3. Genome-wide association study of relative telomere length.

    Science.gov (United States)

    Prescott, Jennifer; Kraft, Peter; Chasman, Daniel I; Savage, Sharon A; Mirabello, Lisa; Berndt, Sonja I; Weissfeld, Joel L; Han, Jiali; Hayes, Richard B; Chanock, Stephen J; Hunter, David J; De Vivo, Immaculata

    2011-05-10

    Telomere function is essential to maintaining the physical integrity of linear chromosomes and healthy human aging. The probability of forming proper telomere structures depends on the length of the telomeric DNA tract. We attempted to identify common genetic variants associated with log relative telomere length using genome-wide genotyping data on 3,554 individuals from the Nurses' Health Study and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial that took part in the National Cancer Institute Cancer Genetic Markers of Susceptibility initiative for breast and prostate cancer. After genotyping 64 independent SNPs selected for replication in additional Nurses' Health Study and Women's Genome Health Study participants, we did not identify genome-wide significant loci; however, we replicated the inverse association of log relative telomere length with the minor allele variant [C] of rs16847897 at the TERC locus (per allele β = -0.03, P = 0.003) identified by a previous genome-wide association study. We did not find evidence for an association with variants at the OBFC1 locus or other loci reported to be associated with telomere length. With this sample size we had >80% power to detect β estimates as small as ±0.10 for SNPs with minor allele frequencies of ≥0.15 at genome-wide significance. However, power is greatly reduced for β estimates smaller than ±0.10, such as those for variants at the TERC locus. In general, common genetic variants associated with telomere length homeostasis have been difficult to detect. Potential biological and technical issues are discussed.

  4. Genome-wide association study of relative telomere length.

    Directory of Open Access Journals (Sweden)

    Jennifer Prescott

    Full Text Available Telomere function is essential to maintaining the physical integrity of linear chromosomes and healthy human aging. The probability of forming proper telomere structures depends on the length of the telomeric DNA tract. We attempted to identify common genetic variants associated with log relative telomere length using genome-wide genotyping data on 3,554 individuals from the Nurses' Health Study and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial that took part in the National Cancer Institute Cancer Genetic Markers of Susceptibility initiative for breast and prostate cancer. After genotyping 64 independent SNPs selected for replication in additional Nurses' Health Study and Women's Genome Health Study participants, we did not identify genome-wide significant loci; however, we replicated the inverse association of log relative telomere length with the minor allele variant [C] of rs16847897 at the TERC locus (per allele β = -0.03, P = 0.003 identified by a previous genome-wide association study. We did not find evidence for an association with variants at the OBFC1 locus or other loci reported to be associated with telomere length. With this sample size we had >80% power to detect β estimates as small as ±0.10 for SNPs with minor allele frequencies of ≥0.15 at genome-wide significance. However, power is greatly reduced for β estimates smaller than ±0.10, such as those for variants at the TERC locus. In general, common genetic variants associated with telomere length homeostasis have been difficult to detect. Potential biological and technical issues are discussed.

  5. Applying functional genomics research to the study of pig reproduction.

    Science.gov (United States)

    Pomp, D; Caetano, A R; Bertani, G R; Gladney, C D; Johnson, R K

    2001-01-01

    Functional genomics is an experimental approach that incorporates genome-wide or system-wide experimentation, expanding the scope of biological investigation from studying single genes to studying potentially all genes at once in a systematic manner. This technology is highly appealing because of its high throughput and relatively low cost. Furthermore, analysis of gene expression using microarrays is likely to be more biologically relevant than the conventional paradigm of reductionism, because it has the potential to uncover new biological connections between genes and biochemical pathways. However, functional genomics is still in its infancy, especially with regard to the study of pig reproduction. Currently, efforts are centred on developing the necessary resources to enable high throughput evaluation and comparison of gene expression. However, it is clear that in the near future functional genomics will be applied on a large scale to study the biology and physiology of reproduction in pigs, and to understand better the complex nature of genetic control over polygenic characteristics, such as ovulation rate and litter size. We can look forward to generating a significant amount of new data on differences in gene expression between genotypes, treatments, or at various temporal and spatial coordinates within a variety of reproductively relevant systems. Along with this capability will be the challenge of collating, analysing and interpreting datasets that are orders of magnitude more extensive and complex than those currently used. Furthermore, integration of functional genomics with traditional genetic approaches and with detailed analysis of the proteome and relevant whole animal phenotypes will be required to make full use of this powerful new experimental paradigm as a beneficial research tool.

  6. Social Studies Progress Monitoring and Intervention for Middle School Students

    Science.gov (United States)

    Beyers, Sarah J.; Lembke, Erica S.; Curs, Bradley

    2013-01-01

    This study examined the technical adequacy of vocabulary-matching curriculum-based measurement (CBM) to identify and monitor the progress of 148 middle school students in social studies. In addition, the effectiveness of a reading comprehension intervention, Collaborative Strategic Reading (Klingner, Vaughn, Dimino, Schumm, & Bryant, 2001),…

  7. Functional genomics studies on the innate immunity of disease vectors

    Institute of Scientific and Technical Information of China (English)

    Luke A. Baton; Lindsey Garver; Zhiyong Xi; George Dimopoulos

    2008-01-01

    The increasing availability of genome sequences and the development of high-throughput techniques for gene expression profiling and functional characterization are transforming the study of innate immunity and other areas of insect biology. Already,functional genomic approaches have enabled a quantum advance in the characterization of mosquito immune responses to malaria parasite infection, and similar high-throughput functional genomic studies of other vector-pathogen interactions can be expected in the near future. The application of microarray-based and other expression analyses provide genomewide transcriptional profiles that can be used to identify insect immune system components that are differentially regulated upon exposure to various classes of pathogens, including many important etiologic agents of human and animal diseases. The role of infection-responsive or other candidate immune genes identified through comparative genomic approaches can then be functionally characterized, either in vivo, for instance in adult mosquitoes, or in vitro using cell lines. In most insect vectors of human pathogens, germ-line transgenesis is still technically difficult and maintenance of multiple transgenic lines logistically demanding.Consequently, transient RNA interference (RNAi)-mediated gene-silencing has rapidly become the method of choice for functional characterization of candidate innate immune genes. The powerful combination of transcriptional profiling in conjunction with assays using RNAi to determine gene function, and identify regulatory pathways, together with downstream cell biological approaches to determine protein localization and interactions,will continue to provide novel insights into the role of insect innate immunity in a variety of vector-pathogen interactions. Here we review advances in functional genomics studies of innate immunity in the insect disease vectors, over the past decade, with a particular focus on the Anopheles mosquito and its

  8. Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study

    DEFF Research Database (Denmark)

    de Vries, Paul S; Sabater-Lleal, Maria; Chasman, Daniel I

    2017-01-01

    An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In...

  9. Comparison of HapMap and 1000 genomes reference panels in a large-scale genome-wide association study

    NARCIS (Netherlands)

    P.S. de Vries (Paul); M. Sabater-Lleal (Maria); D.I. Chasman (Daniel); S. Trompet (Stella); T.S. Ahluwalia (Tarunveer Singh); A. Teumer (Alexander); M.E. Kleber (Marcus); M.-H. Chen (Ming-Huei); J.J. Wang (Jie Jin); J. Attia (John); R.E. Marioni (Riccardo); M. Steri (Maristella); Weng, L.-C. (Lu-Chen); R. Pool (Reńe); V. Grossmann (Vera); J. Brody (Jennifer); C. Venturini (Cristina); T. Tanaka (Toshiko); L.M. Rose (Lynda); C. Oldmeadow (Christopher); J. Mazur (Johanna); S. Basu (Saonli); M. Frånberg (Mattias); Q. Yang (Qiong); S. Ligthart (Symen); J.J. Hottenga (Jouke Jan); A. Rumley (Ann); Mulas, A. (Antonella); A.J. de Craen (Anton); A. Grotevendt (Anne); K.D. Taylor (Kent D.); G. Delgado; A. Kifley (Annette); L.M. Lopez (Lorna); T.L. Berentzen (Tina L.); M. Mangino (Massimo); S. Bandinelli (Stefania); Morrison, A.C. (Alanna C.); A. Hamsten (Anders); G.H. Tofler (Geoffrey); M.P.M. de Maat (Moniek); G. Draisma (Gerrit); G.D. Lowe (Gordon D.); M. Zoledziewska (Magdalena); N. Sattar (Naveed); Lackner, K.J. (Karl J.); U. Völker (Uwe); McKnight, B. (Barbara); J. Huang (Jian); E.G. Holliday (Elizabeth); McEvoy, M.A. (Mark A.); J.M. Starr (John); P.G. Hysi (Pirro); D.G. Hernandez (Dena); W. Guan (Weihua); F. Rivadeneira Ramirez (Fernando); W.L. McArdle (Wendy); P.E. Slagboom (Eline); Zeller, T. (Tanja); B.M. Psaty (Bruce); A.G. Uitterlinden (André); E.J.C. de Geus (Eco); D.J. Stott (David J.); H. Binder (Harald); A. Hofman (Albert); O.H. Franco (Oscar); J.I. Rotter (Jerome I.); L. Ferrucci (Luigi); Spector, T.D. (Tim D.); I.J. Deary (Ian J.); W. März (Winfried); A. Greinacher (Andreas); P.S. Wild (Philipp S.); F. Cucca (Francesco); D.I. Boomsma (Dorret); Watkins, H. (Hugh); Tang, W. (Weihong); P.M. Ridker (Paul); J.W. Jukema; R.J. Scott (Rodney J.); P. Mitchell (Paul); T. Hansen (T.); O'Donnell, C.J. (Christopher J.); Smith, N.L. (Nicholas L.); D.P. Strachan (David P.); A. Dehghan (Abbas)

    2017-01-01

    textabstractAn increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imput

  10. 材料基因组技术前沿进展%Progress on Materials Genome Technology

    Institute of Scientific and Technical Information of China (English)

    向勇; 闫宗楷; 朱焱麟; 张晓琨

    2016-01-01

    Materials genome is an emerging technology to accelerate materials discovery, development, and deployment. In the past two decades, high-throughput materials experimentation tools have been developed and applied successfully to the discovery of a number of materials, ranging from advanced catalysts, dielectrics, electrodes, to high-temperature alloys. Materials computation and database technologies have also made remarkable progresses, particularly represented by the integrated computational materials engineering (ICME) developed in the past decade. Materials genome research integrates high-throughput computation and simulation, high-throughput experimentation, and materials database, throughout the materials discovery-to-deployment process, targeting to cut the materials development time and cost significantly. This review, is trying to give a brief and comprehensive introduction to materials genome technologies, with emphasis on high-throughput materials experimentation, as well as applications of materials computation and database. University of Electronics Science and Technology of China is one of the most active institutes in China in the filed of materials genome research, and some progresses are also highlighted in this review.%材料基因组技术是近年来兴起的材料研究新理念和新方法,是当今世界材料科学与工程领域的最前沿。材料基因组技术的实质是通过融合高通量材料计算设计、高通量材料实验和材料数据库三大组成要素,构建材料设计研发的协同创新网络,加速新材料从发现到应用的全过程。其中,高通量材料实验经过20多年的发展,目前已面向多种形态材料和多种服役性能形成了一系列成功案例,高通量材料计算模拟和材料数据库近几年也取得了较大进展。该文简要回顾了材料基因组技术的主要内容和发展历程,总结了具有代表性的高通量实验技术,以及高通

  11. Insights into kidney diseases from genome-wide association studies.

    Science.gov (United States)

    Wuttke, Matthias; Köttgen, Anna

    2016-09-01

    Over the past decade, genome-wide association studies (GWAS) have considerably improved our understanding of the genetic basis of kidney function and disease. Population-based studies, used to investigate traits that define chronic kidney disease (CKD), have identified >50 genomic regions in which common genetic variants associate with estimated glomerular filtration rate or urinary albumin-to-creatinine ratio. Case-control studies, used to study specific CKD aetiologies, have yielded risk loci for specific kidney diseases such as IgA nephropathy and membranous nephropathy. In this Review, we summarize important findings from GWAS and clinical and experimental follow-up studies. We also compare risk allele frequency, effect sizes, and specificity in GWAS of CKD-defining traits and GWAS of specific CKD aetiologies and the implications for study design. Genomic regions identified in GWAS of CKD-defining traits can contain causal genes for monogenic kidney diseases. Population-based research on kidney function traits can therefore generate insights into more severe forms of kidney diseases. Experimental follow-up studies have begun to identify causal genes and variants, which are potential therapeutic targets, and suggest mechanisms underlying the high allele frequency of causal variants. GWAS are thus a useful approach to advance knowledge in nephrology.

  12. Genomic Comparative Study of Bovine Mastitis Escherichia coli

    Science.gov (United States)

    Kempf, Florent; Slugocki, Cindy; Blum, Shlomo E.; Leitner, Gabriel; Germon, Pierre

    2016-01-01

    Escherichia coli, one of the main causative agents of bovine mastitis, is responsible for significant losses on dairy farms. In order to better understand the pathogenicity of E. coli mastitis, an accurate characterization of E. coli strains isolated from mastitis cases is required. By using phylogenetic analyses and whole genome comparison of 5 currently available mastitis E. coli genome sequences, we searched for genotypic traits specific for mastitis isolates. Our data confirm that there is a bias in the distribution of mastitis isolates in the different phylogenetic groups of the E. coli species, with the majority of strains belonging to phylogenetic groups A and B1. An interesting feature is that clustering of strains based on their accessory genome is very similar to that obtained using the core genome. This finding illustrates the fact that phenotypic properties of strains from different phylogroups are likely to be different. As a consequence, it is possible that different strategies could be used by mastitis isolates of different phylogroups to trigger mastitis. Our results indicate that mastitis E. coli isolates analyzed in this study carry very few of the virulence genes described in other pathogenic E. coli strains. A more detailed analysis of the presence/absence of genes involved in LPS synthesis, iron acquisition and type 6 secretion systems did not uncover specific properties of mastitis isolates. Altogether, these results indicate that mastitis E. coli isolates are rather characterized by a lack of bona fide currently described virulence genes. PMID:26809117

  13. [Strategies of the study on herb genome program].

    Science.gov (United States)

    Chen, Shi-lin; Sun, Yong-zhen; Xu, Jiang; Luo, Hong-mei; Sun, Chao; He, Liu; Cheng, Xiang-lin; Zhang, Bo-li; Xiao, Pei-gen

    2010-07-01

    Herb Genome Program (HerbGP) includes a series of projects on whole genome sequencing (WGS) and post-genomics research of medicinal plants with unique secondary metabolism pathways or/and those of great medical and pharmaceutical importance. In this paper, we systematically discussed the strategy of HerbGP, from species selection, whole-genome sequencing, assembly and bioinformatics analysis, to postgenomics research. HerbGP will push study on Chinese traditional medicines into the front field of life science, by selecting a series of plants with unique secondary metabolism pathways as models and introducing "omics" methods into the research of these medicinal plants. HerbGP will provide great opportunities for China to be the leader in the basic research field of traditional Chinese medicine. HerbGP shall also have significant impacts on the R&D of natural medicines and the development of medicinal farming by analysis of secondary metabolic pathways and selection of cultivars with good agricultural traits.

  14. Genomic Comparative Study of Bovine Mastitis Escherichia coli.

    Science.gov (United States)

    Kempf, Florent; Slugocki, Cindy; Blum, Shlomo E; Leitner, Gabriel; Germon, Pierre

    2016-01-01

    Escherichia coli, one of the main causative agents of bovine mastitis, is responsible for significant losses on dairy farms. In order to better understand the pathogenicity of E. coli mastitis, an accurate characterization of E. coli strains isolated from mastitis cases is required. By using phylogenetic analyses and whole genome comparison of 5 currently available mastitis E. coli genome sequences, we searched for genotypic traits specific for mastitis isolates. Our data confirm that there is a bias in the distribution of mastitis isolates in the different phylogenetic groups of the E. coli species, with the majority of strains belonging to phylogenetic groups A and B1. An interesting feature is that clustering of strains based on their accessory genome is very similar to that obtained using the core genome. This finding illustrates the fact that phenotypic properties of strains from different phylogroups are likely to be different. As a consequence, it is possible that different strategies could be used by mastitis isolates of different phylogroups to trigger mastitis. Our results indicate that mastitis E. coli isolates analyzed in this study carry very few of the virulence genes described in other pathogenic E. coli strains. A more detailed analysis of the presence/absence of genes involved in LPS synthesis, iron acquisition and type 6 secretion systems did not uncover specific properties of mastitis isolates. Altogether, these results indicate that mastitis E. coli isolates are rather characterized by a lack of bona fide currently described virulence genes.

  15. Genome-wide association study identifies five new schizophrenia loci.

    LENUS (Irish Health Repository)

    Ripke, Stephan

    2011-10-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10(-9)), ANK3 (rs10994359, P = 2.5 × 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10(-9)).

  16. Genome-wide association studies in pediatric endocrinology.

    Science.gov (United States)

    Dauber, Andrew; Hirschhorn, Joel N

    2011-01-01

    Genome-wide association (GWA) studies are a powerful tool for understanding the genetic underpinnings of human disease. In this article, we briefly review the role and findings of GWA studies in type 1 diabetes, stature, pubertal timing, obesity, and vitamin D deficiency. We then discuss the present and future implications of these findings with regards to disease prediction, uncovering basic biology, and the development of novel therapeutic agents.

  17. Statistical Approaches in Genome-Wide Association Studies

    OpenAIRE

    Yazdani, Akram

    2014-01-01

    Genome-wide association studies, GWAS, typically contain hundreds of thousands single nucleotide polymorphisms, SNPs, genotyped for few numbers of samples. The aim of these studies is to identify regions harboring SNPs or to predict the outcomes of interest. Since the number of predictors in the GWAS far exceeds the number of samples, it is impossible to analyze the data with classical statistical methods. In the current GWAS, the widely applied methods are based on single marker analysis th...

  18. Progression of diabetic retinopathy: the Beijing Eye Study

    Institute of Scientific and Technical Information of China (English)

    TU Ying; XU Liang; WEI Wen-bin; WANG Shuang; WANG Ya-xing; Jost B Jonas

    2011-01-01

    Background Diabetic retinopathy (DR) has emerged as a leading cause of visual impairment and blindness in the working-aged population worldwide.This study aimed to assess frequency and associated factors of progression of DR in subjects with known diabetes in a population-based setting.Methods The Beijing Eye Study is a population based study performed in Greater Beijing in 2001 and 2006.The present investigation included all subjects with known diabetes mellitus in 2001,who participated in the follow-up examination in 2006.Fundus photographs were assessed.Results The study included 170 subjects; 51 (30%) subjects showed signs of DR in 2001 and were re-examined in 2006,36 (21.2%) subjects (18 subjects with DR present at baseline,18 subjects with newly diagnosed DR in 2006)showed a progression of DR during follow-up.Progression of DR was associated with rural region (odds ratio (OR):5.43,P=0.001) and self-reported arterial hypertension (OR:3.85,P=0.023).In the non-progressive subgroup,presence of DR was associated with different levels of education (<middle school,middle school,college or higher,OR:0.30,P=0.023),treatment modes of diabetes mellitus (OR:10.24,P=0.003) and cataract surgery (OR:9.14,P=0.007).Conclusions In a population-based setting in Greater Beijing,progression of DR occurred in 35% of subjects with pre-existing DR and overall in 21% of subjects with known diabetes within a 5-year period.Progression of DR was significantly associated with rural region and self-reported arterial hypertension.In the stable subjects,presence of DR was significantly associated with poor educational level,insulin treatment of diabetes and cataract surgery.

  19. Whole genome comparative studies between chicken and turkey and their implications for avian genome evolution

    NARCIS (Netherlands)

    Griffin, D.K.; Robertson, L.B.; Tempest, H.G.; Vignal, A.; Fillon, V.; Crooijmans, R.P.M.A.; Groenen, M.A.M.; Deryusheva, S.; Gaginskaya, E.; Carre, W.; Waddington, D.; Talbot, R.; Völker, M.; Masabanda, J.S.; Burt, D.W.

    2008-01-01

    Background Comparative genomics is a powerful means of establishing inter-specific relationships between gene function/location and allows insight into genomic rearrangements, conservation and evolutionary phylogeny. The availability of the complete sequence of the chicken genome has initiated the d

  20. A Review on Progress in QSPR Studies for Surfactants

    OpenAIRE

    Zhengwu Wang; Xiaoyi Zhang; Jiwei Hu

    2010-01-01

    This paper presents a review on recent progress in quantitative structure-property relationship (QSPR) studies of surfactants and applications of various molecular descriptors. QSPR studies on critical micelle concentration (cmc) and surface tension (γ) of surfactants are introduced. Studies on charge distribution in ionic surfactants by quantum chemical calculations and its effects on the structures and properties of the colloids of surfactants are also reviewed. The trends of QSPR studies o...

  1. [Application progress of CRISPR/Cas9 genome editing technology in the treatment of HIV-1 infection].

    Science.gov (United States)

    Han, Yinglun; Li, Qingwei

    2016-01-01

    The goal of gene therapy is to introduce foreign genes into human target cells in a certain way to correct or compensate diseases caused by defective or abnormal genes. Therefore, gene therapy has great practical significance in studying the treatment of persistent or latent HIV-1 infection. At present, the existing methods of gene therapy have some major defects such as limited target site recognition and high frequency of off-targets. The latest research showed that the clustered regularly interspaced short palindromic repeats (CRISPR) /CRISPR-associated nuclease 9 (Cas9) system from bacteria and archaea has been successfully reformed to a targeted genome editing tool. Thus, how to achieve the goal of treating HIV-1 infection by modifying targeted HIV-1 virus genome effectively using the CRISPR/Cas9 system has become a current research focus. Here we review the latest achievements worldwide and briefly introduce applications of the CRISPR/Cas9 genome editing technology in the treatment of HIV-1 infection, including CCR5 gene editing, removal of HIV-1 virus and activation of HIV-1 virus, in order to provide reference for the prevention and treatment of HIV-1 infection.

  2. Progressive genomic convergence of two Helicobacter pylori strains during mixed infection of a patient with chronic gastritis

    Science.gov (United States)

    Cao, Qizhi; Didelot, Xavier; Wu, Zhongbiao; Li, Zongwei; He, Lihua; Li, Yunsheng; Ni, Ming; You, Yuanhai; Lin, Xi; Li, Zhen; Gong, Yanan; Zheng, Minqiao; Zhang, Minli; Liu, Jie; Wang, Weijun; Bo, Xiaochen; Falush, Daniel; Wang, Shengqi; Zhang, Jianzhong

    2015-01-01

    Objective To study the detailed nature of genomic microevolution during mixed infection with multiple Helicobacter pylori strains in an individual. Design We sampled 18 isolates from a single biopsy from a patient with chronic gastritis and nephritis. Whole-genome sequencing was applied to these isolates, and statistical genetic tools were used to investigate their evolutionary history. Results The genomes fall into two clades, reflecting colonisation of the stomach by two distinct strains, and these lineages have accumulated diversity during an estimated 2.8 and 4.2 years of evolution. We detected about 150 clear recombination events between the two clades. Recombination between the lineages is a continuous ongoing process and was detected on both clades, but the effect of recombination in one clade was nearly an order of magnitude higher than in the other. Imputed ancestral sequences also showed evidence of recombination between the two strains prior to their diversification, and we estimate that they have both been infecting the same host for at least 12 years. Recombination tracts between the lineages were, on average, 895 bp in length, and showed evidence for the interspersion of recipient sequences that has been observed in in vitro experiments. The complex evolutionary history of a phage-related protein provided evidence for frequent reinfection of both clades by a single phage lineage during the past 4 years. Conclusions Whole genome sequencing can be used to make detailed conclusions about the mechanisms of genetic change of H. pylori based on sampling bacteria from a single gastric biopsy. PMID:25007814

  3. Exploring Relationships between Host Genome and Microbiome: New Insights from Genome-Wide Association Studies

    Science.gov (United States)

    Abdul-Aziz, Muslihudeen A.; Cooper, Alan; Weyrich, Laura S.

    2016-01-01

    As our understanding of the human microbiome expands, impacts on health and disease continue to be revealed. Alterations in the microbiome can result in dysbiosis, which has now been linked to subsequent autoimmune and metabolic diseases, highlighting the need to identify factors that shape the microbiome. Research has identified that the composition and functions of the human microbiome can be influenced by diet, age, sex, and environment. More recently, studies have explored how human genetic variation may also influence the microbiome. Here, we review several recent analytical advances in this new research area, including those that use genome-wide association studies to examine host genome–microbiome interactions, while controlling for the influence of other factors. We find that current research is limited by small sample sizes, lack of cohort replication, and insufficient confirmatory mechanistic studies. In addition, we discuss the importance of understanding long-term interactions between the host genome and microbiome, as well as the potential impacts of disrupting this relationship, and explore new research avenues that may provide information about the co-evolutionary history of humans and their microorganisms. PMID:27785127

  4. Genetic Control of Canine Leishmaniasis: Genome-Wide Association Study and Genomic Selection Analysis

    OpenAIRE

    Javier Quilez; Verónica Martínez; Woolliams, John A; Armand Sanchez; Ricardo Pong-Wong; Kennedy, Lorna J.; Quinnell, Rupert J.; Ollier, William E R; Xavier Roura; Lluís Ferrer; Laura Altet; Olga Francino

    2012-01-01

    BACKGROUND: The current disease model for leishmaniasis suggests that only a proportion of infected individuals develop clinical disease, while others are asymptomatically infected due to immune control of infection. The factors that determine whether individuals progress to clinical disease following Leishmania infection are unclear, although previous studies suggest a role for host genetics. Our hypothesis was that canine leishmaniasis is a complex disease with multiple loci responsible for...

  5. Public attitudes to the promotion of genomic crop studies in Japan: correlations between genomic literacy, trust, and favourable attitude.

    Science.gov (United States)

    Ishiyama, Izumi; Tanzawa, Tetsuro; Watanabe, Maiko; Maeda, Tadahiko; Muto, Kaori; Tamakoshi, Akiko; Nagai, Akiko; Yamagata, Zentaro

    2012-05-01

    This study aimed to assess public attitudes in Japan to the promotion of genomic selection in crop studies and to examine associated factors. We analysed data from a nationwide opinion survey. A total of 4,000 people were selected from the Japanese general population by a stratified two-phase sampling method, and 2,171 people participated by post; this survey asked about the pros and cons of crop-related genomic studies promotion, examined people's scientific literacy in genomics, and investigated factors thought to be related to genomic literacy and attitude. The relationships were examined using logistic regression models stratified by gender. Survey results showed that 50.0% of respondents approved of the promotion of crop-related genomic studies, while 6.7% disapproved. No correlation was found between literacy and attitude towards promotion. Trust in experts, belief in science, an interest in genomic studies and willingness to purchase new products correlated with a positive attitude towards crop-related genomic studies.

  6. Business Studies within Design and Technology: Continuity and Progression.

    Science.gov (United States)

    Mathews, Maggie; Swainston, David

    1992-01-01

    Explores the placement of business studies courses within design and technology education programs in the United Kingdom. Reports the sense of isolation felt by business educators. Suggests a progression by which economic concepts could be taught on the various grade levels. Calls for further discussion of the proposal. (SG)

  7. A COMPARATIVE STUDY UNDER PROGRESSIVELY FIRST FAILURE CENSORED RAYLEIGH DATA

    Directory of Open Access Journals (Sweden)

    Gyan Prakash

    2015-06-01

    Full Text Available A comparative study presented in this article for two different asymmetric loss functions is based on simulation. Two-parameter Rayleigh model is considered here as the underline model for evaluating the properties of Bayes estimators under progressive first failure censored data. Known and unknown both cases of location parameter are considered here for Bayes estimation of scale parameter.

  8. Preface: Recent progress from networked studies based around MST radar

    Science.gov (United States)

    Hocking, Wayne K.; Lehmann, Volker; Singer, Werner; Yamamoto, Masayuki

    2014-10-01

    Studies of the mesosphere, stratosphere, and troposphere by radar, application of networks, and multi-instrument studies have grown significantly in recent years, and have covered a wide range of areas in technology, fundamental research, and application. This special issue of the Journal of Atmospheric and Solar-Terrestrial Physics on "Recent progress from networked studies based around MST radar" focuses primarily on selected papers presented at the 13th International Workshops on Scientific and Technical Aspects of MST Radar (MST13).

  9. Functional genomic approach to the study of biodiversitywithin Trichoderma

    Institute of Scientific and Technical Information of China (English)

    Monte E; Hermosa M R; González F J; Rey M; Cardoza R E; Gutiérrez S; Delgado Jarana J; Llobell A

    2004-01-01

    @@ Trichoderma is a fungal genus of great and demonstrable biotechnological value, but its genome is poorly surveyed compared with other model microorganisms. Due to their ubiquity and rapid substrate colonization, Trichoderma species have been widely used as biocontrol organisms for agriculture, and their enzyme systems are widely used in industry. Therefore, there is a clear interest to explore beyond the phenotype to exploit the underlying genetic systems using functional genomics tools. The great diversity of species within the Trichoderma genus, the absence of optimized systems for its exploration, and the great variety of genes expressed under a wide range of ambient conditions are the main challenges to consider when starting a comprehensive functional genomics study. An initial project started by three Spanish groups has been extended into the project TRICHOEST, funded by the EU (FP5, QLRT-2001-02032) to target the transcriptome analysis of selected Trichoderma strains with biocontrol potential, in conditions related to antagonism, nutrient stress and plant interactions. Once specific conditions were defined, cDNA libraries were produced and used for EST sequencing. Nine strains from seven Trichoderma species have been considered in this study and an important amount of gene sequence data has been generated, analyzed and used to compare the gene expression in different strains.In parallel to sequencing, genomic expression studies were carried out by means of macro-arrays to identify genes expressed in specific conditions. In silico analysis of DNA sequencing data together with macro-array expression results have lead to a selection based on the potential use of the gene sequences.The selected clone sequences were completed and cloned in appropriate vectors to initiate functional analysis by means of expression studies in homologous and heterologous systems.

  10. A Pooled Genome-Wide Association Study of Asperger Syndrome.

    Directory of Open Access Journals (Sweden)

    Varun Warrier

    Full Text Available Asperger Syndrome (AS is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC, which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448 were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448 lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision.

  11. A Pooled Genome-Wide Association Study of Asperger Syndrome.

    Science.gov (United States)

    Warrier, Varun; Chakrabarti, Bhismadev; Murphy, Laura; Chan, Allen; Craig, Ian; Mallya, Uma; Lakatošová, Silvia; Rehnstrom, Karola; Peltonen, Leena; Wheelwright, Sally; Allison, Carrie; Fisher, Simon E; Baron-Cohen, Simon

    2015-01-01

    Asperger Syndrome (AS) is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC), which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls) of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448) were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448) lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision.

  12. The application of genome editing in studying hearing loss.

    Science.gov (United States)

    Zou, Bing; Mittal, Rahul; Grati, M'hamed; Lu, Zhongmin; Shu, Yilai; Tao, Yong; Feng, Youg; Xie, Dinghua; Kong, Weijia; Yang, Shiming; Chen, Zheng-Yi; Liu, Xuezhong

    2015-09-01

    Targeted genome editing mediated by clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9) technology has emerged as one of the most powerful tools to study gene functions, and with potential to treat genetic disorders. Hearing loss is one of the most common sensory disorders, affecting approximately 1 in 500 newborns with no treatment. Mutations of inner ear genes contribute to the largest portion of genetic deafness. The simplicity and robustness of CRISPR/Cas9-directed genome editing in human cells and model organisms such as zebrafish, mice and primates make it a promising technology in hearing research. With CRISPR/Cas9 technology, functions of inner ear genes can be studied efficiently by the disruption of normal gene alleles through non-homologous-end-joining (NHEJ) mechanism. For genetic hearing loss, CRISPR/Cas9 has potential to repair gene mutations by homology-directed-repair (HDR) or to disrupt dominant mutations by NHEJ, which could restore hearing. Our recent work has shown CRISPR/Cas9-mediated genome editing can be efficiently performed in the mammalian inner ear in vivo. Thus, application of CRISPR/Cas9 in hearing research will open up new avenues for understanding the pathology of genetic hearing loss and provide new routes in the development of treatment to restore hearing. In this review, we describe major methodologies currently used for genome editing. We will highlight applications of these technologies in studies of genetic disorders and discuss issues pertaining to applications of CRISPR/Cas9 in auditory systems implicated in genetic hearing loss.

  13. Mitochondrial genome interrogation for forensic casework and research studies.

    Science.gov (United States)

    Roby, Rhonda K; Sprouse, Marc; Phillips, Nicole; Alicea-Centeno, Alessandra; Shewale, Shantanu; Shore, Sabrina; Paul, Natasha

    2014-04-24

    This unit describes methods used in the analysis of mitochondrial DNA (mtDNA) for forensic and research applications. UNIT describes procedures specifically for forensic casework where the DNA from evidentiary material is often degraded or inhibited. In this unit, protocols are described for quantification of mtDNA before amplification; amplification of the entire control region from high-quality samples as well as procedures for interrogating the whole mitochondrial genome (mtGenome); quantification of mtDNA post-amplification; and, post-PCR cleanup and sequencing. The protocols for amplification were developed for high-throughput databasing applications for forensic DNA testing such as reference samples and population studies. However, these same protocols can be applied to biomedical research such as age-related disease and health disparities research.

  14. Life Sciences Division and Center for Human Genome Studies

    Energy Technology Data Exchange (ETDEWEB)

    Spitzmiller, D.; Bradbury, M.; Cram, S. (comps.)

    1992-05-01

    This report summarizes the research and development activities of Los Alamos National Laboratories Life Sciences Division and biological aspects of the Center for Human Genome Studies for the calendar year 1991. Selected research highlights include: yeast artificial chromosome libraries from flow sorted human chromosomes 16 and 21; distances between the antigen binding sites of three murine antibody subclasses measured using neutron and x-ray scattering; NFCR 10th anniversary highlights; kinase-mediated differences found in the cell cycle regulation of normal and transformed cells; and detecting mutations that cause Gaucher's disease by denaturing gradient gel electrophoresis. Project descriptions include: genomic structure and regulation, molecular structure, cytometry, cell growth and differentiation, radiation biology and carcinogenesis, and pulmonary biology.

  15. Genome-Wide Association Study of Polymorphisms Predisposing to Bronchiolitis

    Science.gov (United States)

    Pasanen, Anu; Karjalainen, Minna K.; Bont, Louis; Piippo-Savolainen, Eija; Ruotsalainen, Marja; Goksör, Emma; Kumawat, Kuldeep; Hodemaekers, Hennie; Nuolivirta, Kirsi; Jartti, Tuomas; Wennergren, Göran; Hallman, Mikko; Rämet, Mika; Korppi, Matti

    2017-01-01

    Bronchiolitis is a major cause of hospitalization among infants. Severe bronchiolitis is associated with later asthma, suggesting a common genetic predisposition. Genetic background of bronchiolitis is not well characterized. To identify polymorphisms associated with bronchiolitis, we conducted a genome-wide association study (GWAS) in which 5,300,000 single nucleotide polymorphisms (SNPs) were tested for association in a Finnish–Swedish population of 217 children hospitalized for bronchiolitis and 778 controls. The most promising SNPs (n = 77) were genotyped in a Dutch replication population of 416 cases and 432 controls. Finally, we used a set of 202 Finnish bronchiolitis cases to further investigate candidate SNPs. We did not detect genome-wide significant associations, but several suggestive association signals (p bronchiolitis. These preliminary findings require further validation in a larger sample size. PMID:28139761

  16. Chronic Periodontitis Genome-wide Association Study in the Hispanic Community Health Study / Study of Latinos.

    Science.gov (United States)

    Sanders, A E; Sofer, T; Wong, Q; Kerr, K F; Agler, C; Shaffer, J R; Beck, J D; Offenbacher, S; Salazar, C R; North, K E; Marazita, M L; Laurie, C C; Singer, R H; Cai, J; Finlayson, T L; Divaris, K

    2017-01-01

    Chronic periodontitis (CP) has a genetic component, particularly its severe forms. Evidence from genome-wide association studies (GWASs) has highlighted several potential novel loci. Here, the authors report the first GWAS of CP among a large community-based sample of Hispanics/Latinos. The authors interrogated a quantitative trait of CP (mean interproximal clinical attachment level determined by full-mouth periodontal examinations) among 10,935 adult participants (mean age: 45 y, range: 18 to 76 y) from the Hispanic Community Health Study / Study of Latinos. Genotyping was done with a custom Illumina Omni2.5M array, and imputation to approximately 20 million single-nucleotide polymorphisms was based on the 1000 Genomes Project phase 1 reference panel. Analyses were based on linear mixed models adjusting for sex, age, study design features, ancestry, and kinship and employed a conventional P evidence of association ( P based sample of Hispanic/Latinos. It identified a genome-wide significant locus that was independently replicated in an African-American population. Identifying this genetic marker offers direction for interrogation in subsequent genomic and experimental studies of CP.

  17. A genome-wide association study of aging.

    Science.gov (United States)

    Walter, Stefan; Atzmon, Gil; Demerath, Ellen W; Garcia, Melissa E; Kaplan, Robert C; Kumari, Meena; Lunetta, Kathryn L; Milaneschi, Yuri; Tanaka, Toshiko; Tranah, Gregory J; Völker, Uwe; Yu, Lei; Arnold, Alice; Benjamin, Emelia J; Biffar, Reiner; Buchman, Aron S; Boerwinkle, Eric; Couper, David; De Jager, Philip L; Evans, Denis A; Harris, Tamara B; Hoffmann, Wolfgang; Hofman, Albert; Karasik, David; Kiel, Douglas P; Kocher, Thomas; Kuningas, Maris; Launer, Lenore J; Lohman, Kurt K; Lutsey, Pamela L; Mackenbach, Johan; Marciante, Kristin; Psaty, Bruce M; Reiman, Eric M; Rotter, Jerome I; Seshadri, Sudha; Shardell, Michelle D; Smith, Albert V; van Duijn, Cornelia; Walston, Jeremy; Zillikens, M Carola; Bandinelli, Stefania; Baumeister, Sebastian E; Bennett, David A; Ferrucci, Luigi; Gudnason, Vilmundur; Kivimaki, Mika; Liu, Yongmei; Murabito, Joanne M; Newman, Anne B; Tiemeier, Henning; Franceschini, Nora

    2011-11-01

    Human longevity and healthy aging show moderate heritability (20%-50%). We conducted a meta-analysis of genome-wide association studies from 9 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for 2 outcomes: (1) all-cause mortality, and (2) survival free of major disease or death. No single nucleotide polymorphism (SNP) was a genome-wide significant predictor of either outcome (p < 5 × 10(-8)). We found 14 independent SNPs that predicted risk of death, and 8 SNPs that predicted event-free survival (p < 10(-5)). These SNPs are in or near genes that are highly expressed in the brain (HECW2, HIP1, BIN2, GRIA1), genes involved in neural development and function (KCNQ4, LMO4, GRIA1, NETO1) and autophagy (ATG4C), and genes that are associated with risk of various diseases including cancer and Alzheimer's disease. In addition to considerable overlap between the traits, pathway and network analysis corroborated these findings. These findings indicate that variation in genes involved in neurological processes may be an important factor in regulating aging free of major disease and achieving longevity.

  18. Sequence imputation of HPV16 genomes for genetic association studies.

    Directory of Open Access Journals (Sweden)

    Benjamin Smith

    Full Text Available BACKGROUND: Human Papillomavirus type 16 (HPV16 causes over half of all cervical cancer and some HPV16 variants are more oncogenic than others. The genetic basis for the extraordinary oncogenic properties of HPV16 compared to other HPVs is unknown. In addition, we neither know which nucleotides vary across and within HPV types and lineages, nor which of the single nucleotide polymorphisms (SNPs determine oncogenicity. METHODS: A reference set of 62 HPV16 complete genome sequences was established and used to examine patterns of evolutionary relatedness amongst variants using a pairwise identity heatmap and HPV16 phylogeny. A BLAST-based algorithm was developed to impute complete genome data from partial sequence information using the reference database. To interrogate the oncogenic risk of determined and imputed HPV16 SNPs, odds-ratios for each SNP were calculated in a case-control viral genome-wide association study (VWAS using biopsy confirmed high-grade cervix neoplasia and self-limited HPV16 infections from Guanacaste, Costa Rica. RESULTS: HPV16 variants display evolutionarily stable lineages that contain conserved diagnostic SNPs. The imputation algorithm indicated that an average of 97.5±1.03% of SNPs could be accurately imputed. The VWAS revealed specific HPV16 viral SNPs associated with variant lineages and elevated odds ratios; however, individual causal SNPs could not be distinguished with certainty due to the nature of HPV evolution. CONCLUSIONS: Conserved and lineage-specific SNPs can be imputed with a high degree of accuracy from limited viral polymorphic data due to the lack of recombination and the stochastic mechanism of variation accumulation in the HPV genome. However, to determine the role of novel variants or non-lineage-specific SNPs by VWAS will require direct sequence analysis. The investigation of patterns of genetic variation and the identification of diagnostic SNPs for lineages of HPV16 variants provides a valuable

  19. Genome-wide Association Studies from the Cancer Genetic Markers of Susceptibility (CGEMS) Initiative | Office of Cancer Genomics

    Science.gov (United States)

    CGEMS identifies common inherited genetic variations associated with a number of cancers, including breast and prostate. Data from these genome-wide association studies (GWAS) are available through the Division of Cancer Epidemiology & Genetics website.

  20. Somatic Genomics and Clinical Features of Lung Adenocarcinoma: A Retrospective Study

    Science.gov (United States)

    Zhu, Bin; Wang, Mingyi; Pariscenti, Gianluca; Jones, Kristine; Bouk, Aaron J.; Boland, Joseph; Luke, Brian T.; Song, Lei; Duan, Jubao; Liu, Pengyuan; Kohno, Takashi; Chen, Qingrong; Meerzaman, Daoud; Marconett, Crystal; Mills, Ian; Caporaso, Neil E.; Gail, Mitchell H.; Pesatori, Angela C.; Consonni, Dario; Bertazzi, Pier Alberto; Chanock, Stephen J.; Landi, Maria Teresa

    2016-01-01

    Background Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and has a high risk of distant metastasis at every disease stage. We aimed to characterize the genomic landscape of LUAD and identify mutation signatures associated with tumor progression. Methods and Findings We performed an integrative genomic analysis, incorporating whole exome sequencing (WES), determination of DNA copy number and DNA methylation, and transcriptome sequencing for 101 LUAD samples from the Environment And Genetics in Lung cancer Etiology (EAGLE) study. We detected driver genes by testing whether the nonsynonymous mutation rate was significantly higher than the background mutation rate and replicated our findings in public datasets with 724 samples. We performed subclonality analysis for mutations based on mutant allele data and copy number alteration data. We also tested the association between mutation signatures and clinical outcomes, including distant metastasis, survival, and tumor grade. We identified and replicated two novel candidate driver genes, POU class 4 homeobox 2 (POU4F2) (mutated in 9 [8.9%] samples) and ZKSCAN1 (mutated in 6 [5.9%] samples), and characterized their major deleterious mutations. ZKSCAN1 was part of a mutually exclusive gene set that included the RTK/RAS/RAF pathway genes BRAF, EGFR, KRAS, MET, and NF1, indicating an important driver role for this gene. Moreover, we observed strong associations between methylation in specific genomic regions and somatic mutation patterns. In the tumor evolution analysis, four driver genes had a significantly lower fraction of subclonal mutations (FSM), including TP53 (p = 0.007), KEAP1 (p = 0.012), STK11 (p = 0.0076), and EGFR (p = 0.0078), suggesting a tumor initiation role for these genes. Subclonal mutations were significantly enriched in APOBEC-related signatures (p < 2.5×10−50). The total number of somatic mutations (p = 0.0039) and the fraction of transitions (p = 5.5×10−4) were

  1. A salmonid EST genomic study: genes, duplications, phylogeny and microarrays

    Directory of Open Access Journals (Sweden)

    Brahmbhatt Sonal

    2008-11-01

    Full Text Available Abstract Background Salmonids are of interest because of their relatively recent genome duplication, and their extensive use in wild fisheries and aquaculture. A comprehensive gene list and a comparison of genes in some of the different species provide valuable genomic information for one of the most widely studied groups of fish. Results 298,304 expressed sequence tags (ESTs from Atlantic salmon (69% of the total, 11,664 chinook, 10,813 sockeye, 10,051 brook trout, 10,975 grayling, 8,630 lake whitefish, and 3,624 northern pike ESTs were obtained in this study and have been deposited into the public databases. Contigs were built and putative full-length Atlantic salmon clones have been identified. A database containing ESTs, assemblies, consensus sequences, open reading frames, gene predictions and putative annotation is available. The overall similarity between Atlantic salmon ESTs and those of rainbow trout, chinook, sockeye, brook trout, grayling, lake whitefish, northern pike and rainbow smelt is 93.4, 94.2, 94.6, 94.4, 92.5, 91.7, 89.6, and 86.2% respectively. An analysis of 78 transcript sets show Salmo as a sister group to Oncorhynchus and Salvelinus within Salmoninae, and Thymallinae as a sister group to Salmoninae and Coregoninae within Salmonidae. Extensive gene duplication is consistent with a genome duplication in the common ancestor of salmonids. Using all of the available EST data, a new expanded salmonid cDNA microarray of 32,000 features was created. Cross-species hybridizations to this cDNA microarray indicate that this resource will be useful for studies of all 68 salmonid species. Conclusion An extensive collection and analysis of salmonid RNA putative transcripts indicate that Pacific salmon, Atlantic salmon and charr are 94–96% similar while the more distant whitefish, grayling, pike and smelt are 93, 92, 89 and 86% similar to salmon. The salmonid transcriptome reveals a complex history of gene duplication that is

  2. Genome-wide association studies and contribution to cardiovascular physiology.

    Science.gov (United States)

    Munroe, Patricia B; Tinker, Andrew

    2015-09-01

    The study of family pedigrees with rare monogenic cardiovascular disorders has revealed new molecular players in physiological processes. Genome-wide association studies of complex traits with a heritable component may afford a similar and potentially intellectually richer opportunity. In this review we focus on the interpretation of genetic associations and the issue of causality in relation to known and potentially new physiology. We mainly discuss cardiometabolic traits as it reflects our personal interests, but the issues pertain broadly in many other disciplines. We also describe some of the resources that are now available that may expedite follow up of genetic association signals into observations on causal mechanisms and pathophysiology.

  3. [Genome-wide association study for adolescent idiopathic scoliosis].

    Science.gov (United States)

    Ogura, Yoji; Kou, Ikuyo; Scoliosis, Japan; Matsumoto, Morio; Watanabe, Kota; Ikegawa, Shiro

    2016-04-01

    Adolescent idiopathic scoliosis(AIS)is a polygenic disease. Genome-wide association studies(GWASs)have been performed for a lot of polygenic diseases. For AIS, we conducted GWAS and identified the first AIS locus near LBX1. After the discovery, we have extended our study by increasing the numbers of subjects and SNPs. In total, our Japanese GWAS has identified four susceptibility genes. GWASs for AIS have also been performed in the USA and China, which identified one and three susceptibility genes, respectively. Here we review GWASs in Japan and abroad and functional analysis to clarify the pathomechanism of AIS.

  4. A Review on Progress in QSPR Studies for Surfactants

    Directory of Open Access Journals (Sweden)

    Zhengwu Wang

    2010-03-01

    Full Text Available This paper presents a review on recent progress in quantitative structure-property relationship (QSPR studies of surfactants and applications of various molecular descriptors. QSPR studies on critical micelle concentration (cmc and surface tension (γ of surfactants are introduced. Studies on charge distribution in ionic surfactants by quantum chemical calculations and its effects on the structures and properties of the colloids of surfactants are also reviewed. The trends of QSPR studies on cloud point (for nonionic surfactants, biodegradation potential and some other properties of surfactants are evaluated .

  5. Study Progress on Tissue Culture of Maize Mature Embryo

    Science.gov (United States)

    Wang, Hongzhen; Cheng, Jun; Cheng, Yanping; Zhou, Xioafu

    It has been paid more and more attention on maize tissue culture as it is a basic work in maize genetic transformation, especially huge breakthrough has been made in maize tissue culture utilizing mature embryos as explants in the recent years. This paper reviewed the study progress on maize tissue culture and plant regeneration utilizing mature embryos as explants from callus induction, subculture, plant regeneration and browning reduction and so on.

  6. Progress in Studies of Geomagnetic Navigation of Animals

    Institute of Scientific and Technical Information of China (English)

    Tian Lanxiang; Pan Yongxin; Lin Wei; Wang Yinan; Zhang Shuyi

    2005-01-01

    @@ The geomagnetic field may play a key role in orientation and navigation of many long-distance migratory animals. Taking homing and migrating birds as examples, this paper reviews recent progress in studies of geomagnetic "compass" of animals.Moreover, we propose to address two aspects in future geomagnetic orientation research: ( 1 ) what are the true components of the "map"? (2) What are the magneto-receptors and which brain areas acquire and process the geomagnetic field information ?

  7. Invited review: Genomic analysis of data from physiological studies.

    Science.gov (United States)

    Garrick, D J; Baumgard, L H; Neibergs, H L

    2012-02-01

    Physiology deals with the functions of living organisms and their systems, and its scientific endeavors can be viewed as having temporally occurred in 3 phases. The first phase of physiology studies focused on determining the functions of particular organs and tissues and their functional differences according to physiological status. The second phase of studies focused on characterizing differences in these functions according to the environment, or productivity. The third phase of studies focuses on determining the physiological causes of differences in productivity. Distinguishing cause from effect in physiological systems of inter-related processes is problematic, such that science has struggled to identify the root physiological mechanisms and their role in the network of genes leading to differences in productivity. Genomics is the study of the entire genome and provides powerful new tools that will accelerate third-phase discoveries of causal physiological processes. That research exploits information on DNA polymorphisms known as markers, complete DNA sequence, RNA sequence, and RNA expression in particular tissues at specific life stages. Physiologists can determine the genetic cause of mutant animals, identify genetic differences between cases and controls, and identify genes responsible for differences in performance between average and above-average animals. In some species, physiologists can leverage genomic data being used to predict genetic merit in elite seedstock populations, as a starting point to identify genes that will then motivate detailed physiological studies in the organs or tissues and stages of life in which those genes are expressed. Such work will increase our knowledge of biology and may lead to novel approaches to manipulate animal performance.

  8. The Global Invertebrate Genomics Alliance (GIGA). 2014. Developing Community Resources to Study Diverse Invertebrate Genomes

    NARCIS (Netherlands)

    Pomponi, S.A.

    2014-01-01

    Over 95% of all metazoan (animal) species comprise the “invertebrates,” but very few genomes from these organisms have been sequenced. We have, therefore, formed a “Global Invertebrate Genomics Alliance” (GIGA). Our intent is to build a collaborative network of diverse scientists to tackle major cha

  9. The Global Invertebrate Genomics Alliance (GIGA). 2014. Developing Community Resources to Study Diverse Invertebrate Genomes

    NARCIS (Netherlands)

    Pomponi, S.A.

    2014-01-01

    Over 95% of all metazoan (animal) species comprise the “invertebrates,” but very few genomes from these organisms have been sequenced. We have, therefore, formed a “Global Invertebrate Genomics Alliance” (GIGA). Our intent is to build a collaborative network of diverse scientists to tackle major

  10. The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation

    Science.gov (United States)

    The establishment of the epigenetic mark H4K20me1 (monomethylation of H4K20) by PR-Set7 during G2/M directly impacts S-phase progression and genome stability. However, the mechanisms involved in the regulation of this event are not well understood. Here we show that SirT2 regulates H4K20me1 depositi...

  11. 吸虫线粒体基因研究进展%Research progress on trematode mitochodrial genome

    Institute of Scientific and Technical Information of China (English)

    王曼; 王光西; 张锡林

    2011-01-01

    Trematode belongs to Platyhelminthes' s trematoda,it' s an important class of parasitic zoonosis,not only seriously threatening human health,but also affecting the production of aquaculture and livestock industry.The study on mitochondrial genome is one of the most essential part in molecular biology.This article focused on the composition of trematode mitochondrial genome,structure and significance of mitochondrial DNA research and the applications of the trematode mitochondrial DNA research.%吸虫属于扁形动物门吸虫纲,是一类重要的人兽共患蠕虫病病原,对人体危害很大,也严重影响水产业和畜牧业的发展.分子生物学方法是研究吸虫的重要工具.该文对吸虫线粒体分子生物学的研究进行总结,重点介绍吸虫线粒体基因的组成和结构特点、吸虫线粒体基因的研究意义及吸虫线粒体基因组研究的应用前景.

  12. Chromosome region-specific libraries for human genome analysis. Final progress report, 1 March 1991--28 February 1994

    Energy Technology Data Exchange (ETDEWEB)

    Kao, F.T.

    1994-04-01

    The objectives of this grant proposal include (1) development of a chromosome microdissection and PCR-mediated microcloning technology, (2) application of this microtechnology to the construction of region-specific libraries for human genome analysis. During this grant period, the authors have successfully developed this microtechnology and have applied it to the construction of microdissection libraries for the following chromosome regions: a whole chromosome 21 (21E), 2 region-specific libraries for the long arm of chromosome 2, 2q35-q37 (2Q1) and 2q33-q35 (2Q2), and 4 region-specific libraries for the entire short arm of chromosome 2, 2p23-p25 (2P1), 2p21-p23 (2P2), 2p14-p16 (wP3) and 2p11-p13 (2P4). In addition, 20--40 unique sequence microclones have been isolated and characterized for genomic studies. These region-specific libraries and the single-copy microclones from the library have been used as valuable resources for (1) isolating microsatellite probes in linkage analysis to further refine the disease locus; (2) isolating corresponding clones with large inserts, e.g. YAC, BAC, P1, cosmid and phage, to facilitate construction of contigs for high resolution physical mapping; and (3) isolating region-specific cDNA clones for use as candidate genes. These libraries are being deposited in the American Type Culture Collection (ATCC) for general distribution.

  13. Genomic amplification of the human telomerase gene (hTERC associated with human papillomavirus is related to the progression of uterine cervical dysplasia to invasive cancer

    Directory of Open Access Journals (Sweden)

    Liu Hongqian

    2012-10-01

    Full Text Available Abstract Background Human papillomavirus (HPV infection plays an etiological role in the development of cervical dysplasia and cancer. Amplification of human telomerase gene (hTERC and over expression of telomerase were found to be associated with cervical tumorigenesis. This study was performed to analyze genomic amplification of hTERC gene, telomerase activity in association with HPV infection in different stages of cervical intraepithelial neoplasia (CIN and cervical cancer. We were studying the role of hTERC in the progression of uterine cervical dysplasia to invasive cancer, and proposed an adjunct method for cervical cancer screening. Methods Exfoliated cervical cells were collected from 114 patients with non neoplastic lesion (NNL, n=27, cervical intraepithelial neoplasia (CIN1, n=26, CIN2, n=16, CIN3, n=24 and cervical carcinoma (CA, n=21, and analyzed for amplification of hTERC with two-color fluorescence in situ hybridization (FISH probe and HPV-DNA with Hybrid Capture 2. From these patients, 53 were taken biopsy to analyze telomerase activity by telomeric repeat amplification protocol (TRAP and expression of human telomerase reverse transcriptase (hTERT, with immunohistochemistry (IHC. All biopsies were clinically confirmed by phathologists. Results Amplification of hTERC was significantly associated with the histologic diagnoses (p Conclusions hTERC ampliffication can be detected with FISH technique on exfoliated cervical cells. Amplification of hTERC and HPV infection are associated with more progressive CIN3 and CA. The testing of hTERC amplification might be a supplementary to cytology screening and HPV test, especially high-risk patients. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1857134686755648.

  14. Genome-wide association study and premature ovarian failure.

    Science.gov (United States)

    Christin-Maitre, S; Tachdjian, G

    2010-05-01

    Premature ovarian failure (POF) is defined as an amenorrhea for more than 4months, associated with elevated gonadotropins, usually higher than 20mIU/ml, occurring in a woman before the age of 40. Some candidate genes have been identified in the past 15years, such as FOXL2, FSHR, BMP15, GDF9, Xfra premutation. However, POF etiology remains unknown in more than 90% of cases. The first strategy to identify candidate gene, apart from studying genes involved in ovarian failure in animal models, relies on the study of X chromosome deletions and X;autosome translocations in patients. The second strategy is based on linkage analysis, the third one on Comparative Genomic Hybridization (CGH) array. The latest strategy relies on Genome-Wide Association Studies (GWAS). This technique consists in screening single nucleotide polymorphisms (SNPs) in patients and controls. So far, three studies have been performed and have identified different loci potentially linked to POF, such as PTHB1 and ADAMTS19. However, replications in independent cohorts need to be performed. GWAS studies on large cohorts of women with POF should find new candidate genes in the near future.

  15. Planning and executing a genome wide association study (GWAS).

    Science.gov (United States)

    Sale, Michèle M; Mychaleckyj, Josyf C; Chen, Wei-Min

    2009-01-01

    In recent years, genome-wide association approaches have proven a powerful and successful strategy to identify genetic contributors to complex traits, including a number of endocrine disorders. Their success has meant that genome wide association studies (GWAS) are fast becoming the default study design for discovery of new genetic variants that influence a clinical trait or phenotype. This chapter focuses on a number of key elements that require consideration for the successful conduct of a GWAS. Although many of the considerations are common to any genetic study, the greater cost, extreme multiple testing, and greater openness to data sharing require specific awareness and planning by investigators. In the section on designing a GWAS, we reflect on ethical considerations, study design, selection of phenotype/s, power considerations, sample tracking and storage issues, and genotyping product selection. During execution, important considerations include DNA quantity and preparation, genotyping methods, quality control checks of genotype data, in silico genotyping (imputation), tests of association, and replication of association signals. Although the field of human genetics is rapidly evolving, recent experiences can help guide an investigator in making practical and methodological choices that will eventually determine the overall quality of GWAS results. Given the investment to recruit patient populations or cohorts that are powered for a GWAS, and the still substantial costs associated with genotyping, it is helpful to be aware of these aspects to maximize the likelihood of success, especially where there is an opportunity for implementing them prospectively.

  16. GenomicusPlants: a web resource to study genome evolution in flowering plants.

    Science.gov (United States)

    Louis, Alexandra; Murat, Florent; Salse, Jérôme; Crollius, Hugues Roest

    2015-01-01

    Comparative genomics combined with phylogenetic reconstructions are powerful approaches to study the evolution of genes and genomes. However, the current rapid expansion of the volume of genomic information makes it increasingly difficult to interrogate, integrate and synthesize comparative genome data while taking into account the maximum breadth of information available. GenomicusPlants (http://www.genomicus.biologie.ens.fr/genomicus-plants) is an extension of the Genomicus webserver that addresses this issue by allowing users to explore flowering plant genomes in an intuitive way, across the broadest evolutionary scales. Extant genomes of 26 flowering plants can be analyzed, as well as 23 ancestral reconstructed genomes. Ancestral gene order provides a long-term chronological view of gene order evolution, greatly facilitating comparative genomics and evolutionary studies. Four main interfaces ('views') are available where: (i) PhyloView combines phylogenetic trees with comparisons of genomic loci across any number of genomes; (ii) AlignView projects loci of interest against all other genomes to visualize its topological conservation; (iii) MatrixView compares two genomes in a classical dotplot representation; and (iv) Karyoview visualizes chromosome karyotypes 'painted' with colours of another genome of interest. All four views are interconnected and benefit from many customizable features.

  17. Research progress on the targeted genome modification%基因组靶向修饰技术研究进展

    Institute of Scientific and Technical Information of China (English)

    周阳; 袁少飞; 蒋廷亚; 韩邦兴; 高力; 陈乃富

    2015-01-01

    Targeted genome modification technology is one of the important methods to study genes′function, which also can be used for the treatment of human diseases at the same time.It is becoming a hot field of biology research in recent years.Because of its low efficiency and toxicity, traditional targeted modification technology will be replaced by a more efficient and safer technology.Thus three generations of targeted genome modification technologies have been developed.It includes ZFN, TALEN and CRISPR/Cas9.These three techniques overcome the defects of traditional technology.Here, we discuss the research progress in the structure, mechanism and application of these three technologies, especially newly developed CRISPR/Cas9.Finally, the three generations of genome modifi-cation techniques are compared.%基因组靶向修饰技术是研究基因功能的重要方法之一,该技术也被用于人类疾病的治疗上,从而成为近来生物学研究的热点。传统的靶向修饰技术由于其效率低、有毒性等缺点注定其将要被更高效、安全的技术所取代,因此产生了后来的三代基因组靶向修饰技术:锌指核酸酶( Zinc finger nuclease, ZFN)、类转录激活因子效应物核酸酶( Transcription activator-like effector nuclease, TALEN)和常间回文重复序列丛集关联蛋白系统( Clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins 9, CRISPR/Cas9)。这3种技术在克服传统技术缺陷的基础上,也针对其上一代技术的缺陷进行了自身的改善。对三代基因组靶向修饰技术,尤其最近发展起来的CRISPR/Cas9的结构组成、作用原理和基因定点修饰中的应用进行阐述,最后对三代基因组靶向修饰技术进行比较。

  18. Progress in glial cell studies in some laboratories in China

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Glial cells in the central nervous system(CNS) consist of a heterogeneous population of cell types,each characterized by distinct morphological features,physiological properties,and specific markers.In contrast to the previous view that glial cells were passive elements in the brain,accumulating evidence suggests that glial cells are active participants in various brain functions and brain disorders.This review summarizes recent progress of glial cell studies from several groups in China,ranging from studies about the mechanisms of neuron-glia crosstalking to investigations on the roles of glial cells in various CNS disorders.

  19. Recent progress in high-pressure studies on organic conductors

    Directory of Open Access Journals (Sweden)

    Syuma Yasuzuka and Keizo Murata

    2009-01-01

    Full Text Available Recent high-pressure studies of organic conductors and superconductors are reviewed. The discovery of the highest Tc superconductivity among organics under high pressure has triggered the further progress of the high-pressure research. Owing to this finding, various organic conductors with the strong electron correlation were investigated under high pressures. This review includes the pressure techniques using the cubic anvil apparatus, as well as high-pressure studies of the organic conductors up to 10 GPa showing extraordinary temperature and pressure dependent transport phenomena.

  20. Genome-Wide Association Studies of the Human Gut Microbiota.

    Directory of Open Access Journals (Sweden)

    Emily R Davenport

    Full Text Available The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both. These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%. For example, we identified an association between a taxon known to affect obesity (genus Akkermansia and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10-7. Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut.

  1. Attitudes towards personal genomics among older Swiss adults: An exploratory study

    Directory of Open Access Journals (Sweden)

    Laura Mählmann

    2016-03-01

    Conclusion: This study indicates a relatively positive overall attitude towards personal genomic testing among older Swiss adults, a group not typically represented in surveys about personal genomics. Genomic data of older adults can be highly relevant to late life health and maintenance of quality of life. In addition they can be an invaluable source for better understanding of longevity, health and disease. Understanding the attitudes of this population towards genomic analyses, although important, remains under-examined.

  2. Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease

    NARCIS (Netherlands)

    Ji, Sun-Gou; Juran, Brian D.; Mucha, Soeren; Folseraas, Trine; Jostins, Luke; Melum, Espen; Kumasaka, Natsuhiko; Atkinson, Elizabeth J.; Schlicht, Erik M; Liu, Jimmy Z.; Shah, Tejas; Gutierrez-Achury, Javier; Boberg, Kirsten M.; Bergquist, Annika; Vermeire, Severine; Eksteen, Bertus; Durie, Peter R.; Farkkila, Martti; Mueller, Tobias; Schramm, Christoph; Sterneck, Martina; Weismueller, Tobias J.; Gotthardt, Daniel Nils; Ellinghaus, David; Braun, Felix; Teufel, Andreas; Laudes, Mattias; Lieb, Wolfgang; Jacobs, Gunnar; Beuers, Ulrich; Weersma, Rinse K.; Wijmenga, Cisca; Marschall, Hanns-Ulrich; Milkiewicz, Piotr; Pares, Albert; Kontula, Kimmo; Chazouilleres, Olivier; Invernizzi, Pietro; Goode, Elizabeth; Spiess, Kelly; Moore, Carmel; Sambrook, Jennifer; Ouwehand, Willem H.; Roberts, David J; Danesh, John; Floreani, Annarosa; Gulamhusein, Aliya F; Eaton, John E; Schreiber, Stefan; Coltescu, Catalina; Bowlus, Christopher L.; Luketic, Velimir A.; Odin, Joseph A; Chopra, Kapil B; Kowdley, Kris V; Chalasani, Naga; Manns, Michael P.; Srivastava, Brijesh; Mells, George; Sandford, Richard N.; Alexander, Graeme; Gaffney, Daniel J; Chapman, Roger W.; Hirschfield, Gideon M.; de Andrade, Mariza; Rushbrook, Simon M.; Franke, Andre; Karlsen, Tom H.; Lazaridis, Konstantinos N.; Anderson, Carl A.

    Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; similar to 75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified

  3. Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease

    NARCIS (Netherlands)

    Ji, Sun-Gou; Juran, Brian D; Mucha, Sören; Folseraas, Trine; Jostins, Luke; Melum, Espen; Kumasaka, Natsuhiko; Atkinson, Elizabeth J; Schlicht, Erik M; Liu, Jimmy Z; Shah, Tejas; Gutierrez-Achury, Javier; Boberg, Kirsten M; Bergquist, Annika; Vermeire, Severine; Eksteen, Bertus; Durie, Peter R; Farkkila, Martti; Müller, Tobias; Schramm, Christoph; Sterneck, Martina; Weismüller, Tobias J; Gotthardt, Daniel N; Ellinghaus, David; Braun, Felix; Teufel, Andreas; Laudes, Mattias; Lieb, Wolfgang; Jacobs, Gunnar; Beuers, Ulrich; Weersma, Rinse K; Wijmenga, Cisca; Marschall, Hanns-Ulrich; Milkiewicz, Piotr; Pares, Albert; Kontula, Kimmo; Chazouillères, Olivier; Invernizzi, Pietro; Goode, Elizabeth; Spiess, Kelly; Moore, Carmel; Sambrook, Jennifer; Ouwehand, Willem H; Roberts, David J; Danesh, John; Floreani, Annarosa; Gulamhusein, Aliya F; Eaton, John E; Schreiber, Stefan; Coltescu, Catalina; Bowlus, Christopher L; Luketic, Velimir A; Odin, Joseph A; Chopra, Kapil B; Kowdley, Kris V; Chalasani, Naga; Manns, Michael P; Srivastava, Brijesh; Mells, George; Sandford, Richard N; Alexander, Graeme; Gaffney, Daniel J; Chapman, Roger W; Hirschfield, Gideon M; de Andrade, Mariza; Rushbrook, Simon M; Franke, Andre; Karlsen, Tom H; Lazaridis, Konstantinos N; Anderson, Carl A

    2016-01-01

    Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; ∼75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new ge

  4. A genome-wide association study of female sexual dysfunction.

    Directory of Open Access Journals (Sweden)

    Andrea Burri

    Full Text Available BACKGROUND: Female sexual dysfunction (FSD is an important but controversial problem with serious negative impact on women's quality of life. Data from twin studies have shown a genetic contribution to the development and maintenance of FSD. METHODOLOGY/PRINCIPAL FINDINGS: We performed a genome-wide association study (GWAS on 2.5 million single-nucleotide polymorphisms (SNPs in 1,104 female twins (25-81 years of age in a population-based register and phenotypic data on lifelong sexual functioning. Although none reached conventional genome-wide level of significance (10 × -8, we found strongly suggestive associations with the phenotypic dimension of arousal (rs13202860, P = 1.2 × 10(-7; rs1876525, P = 1.2 × 10(-7; and rs13209281 P = 8.3 × 10(-7 on chromosome 6, around 500 kb upstream of the locus HTR1E (5-hydroxytryptamine receptor 1E locus, related to the serotonin brain pathways. We could not replicate previously reported candidate SNPs associated with FSD in the DRD4, 5HT2A and IL-1B loci. CONCLUSIONS/SIGNIFICANCE: We report the first GWAS of FSD symptoms in humans. This has pointed to several "risk alleles" and the implication of the serotonin and GABA pathways. Ultimately, understanding key mechanisms via this research may lead to new FSD treatments and inform clinical practice and developments in psychiatric nosology.

  5. From genome-wide arrays to tailor-made biomarker readout - Progress towards routine analysis of skin sensitizing chemicals with GARD.

    Science.gov (United States)

    Forreryd, Andy; Zeller, Kathrin S; Lindberg, Tim; Johansson, Henrik; Lindstedt, Malin

    2016-12-01

    Allergic contact dermatitis (ACD) initiated by chemical sensitizers is an important public health concern. To prevent ACD, it is important to identify chemical allergens to limit the use of such compounds in various products. EU legislations, as well as increased mechanistic knowledge of skin sensitization have promoted development of non-animal based approaches for hazard classification of chemicals. GARD is an in vitro testing strategy based on measurements of a genomic biomarker signature. However, current GARD protocols are optimized for identification of predictive biomarker signatures, and not suitable for standardized screening. This study describes improvements to GARD to progress from biomarker discovery into a reliable and cost-effective assay for routine testing. Gene expression measurements were transferred to NanoString nCounter platform, normalization strategy was adjusted to fit serial arrival of testing substances, and a novel strategy to correct batch variations was presented. When challenging GARD with 29 compounds, sensitivity, specificity and accuracy could be estimated to 94%, 83% and 90%, respectively. In conclusion, we present a GARD workflow with improved sample capacity, retained predictive performance, and in a format adapted to standardized screening. We propose that GARD is ready to be considered as part of an integrated testing strategy for skin sensitization.

  6. Polygenic risk accelerates the developmental progression to heavy, persistent smoking and nicotine dependence: Evidence from a 4-Decade Longitudinal Study

    Science.gov (United States)

    Moffitt, Terrie E; Baker, Timothy B; Biddle, Andrea K; Evans, James P; Harrington, HonaLee; Houts, Renate; Meier, Madeline; Sugden, Karen; Williams, Benjamin; Poulton, Richie; Caspi, Avshalom

    2013-01-01

    OBJECTIVE To test how genomic loci identified in genome-wide association studies (GWAS) influence the developmental progression of smoking behavior. DESIGN A 38-year prospective longitudinal study of a representative birth-cohort. SETTING The Dunedin Multidisciplinary Health and Development Study, New Zealand. PARTICIPANTS N=1037 male and female study members. MAIN EXPOSURES We assessed genetic risk with a multi-locus genetic risk score (GRS). The GRS was composed of single-nucleotide polymorphisms identified in three meta-analyses of GWAS of smoking quantity phenotypes. OUTCOME MEASURES Smoking initiation, conversion to daily smoking, progression to heavy smoking, nicotine dependence (Fagerstrom Test of Nicotine Dependence), and cessation difficulties were evaluated at eight assessments spanning ages 11-38 years. RESULTS Genetic risk score was unrelated to smoking initiation. However, individuals at higher genetic risk were more likely to convert to daily smoking as teenagers, progressed more rapidly from smoking initiation to heavy smoking, persisted longer in smoking heavily, developed nicotine dependence more frequently, were more reliant on smoking to cope with stress, and were more likely to fail in their cessation attempts. Further analysis revealed that two adolescent developmental phenotypes—early conversion to daily smoking and rapid progression to heavy smoking--mediated associations between the genetic risk score and mature phenotypes of persistent heavy smoking, nicotine dependence, and cessation failure. The genetic risk score predicted smoking risk over and above family history. CONCLUSIONS Initiatives that disrupt the developmental progression of smoking behavior among adolescents may mitigate genetic risks for developing adult smoking problems. Future genetic research may maximize discovery potential by focusing on smoking behavior soon after smoking initiation and by studying young smokers. PMID:23536134

  7. Genome-wide association studies in pharmacogenomics of antidepressants.

    Science.gov (United States)

    Lin, Eugene; Lane, Hsien-Yuan

    2015-01-01

    Major depressive disorder (MDD) is one of the most common psychiatric disorders worldwide. Doctors must prescribe antidepressants based on educated guesses due to the fact that it is unmanageable to predict the effectiveness of any particular antidepressant in an individual patient. With the recent advent of scientific research, the genome-wide association study (GWAS) is extensively employed to analyze hundreds of thousands of single nucleotide polymorphisms by high-throughput genotyping technologies. In addition to the candidate-gene approach, the GWAS approach has recently been utilized to investigate the determinants of antidepressant response to therapy. In this study, we reviewed GWAS studies, their limitations and future directions with respect to the pharmacogenomics of antidepressants in MDD.

  8. Genome-wide association study of serum selenium concentrations

    DEFF Research Database (Denmark)

    Gong, Jian; Hsu, Li; Harrison, Tabitha

    2013-01-01

    Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated...... this hypothesis. Therefore, we conducted a two-stage genome-wide association study to identify genetic variants associated with serum selenium concentrations in 1203 European descents from two cohorts: the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening and the Women’s Health Initiative (WHI). We...... tested association between 2,474,333 single nucleotide polymorphisms (SNPs) and serum selenium concentrations using linear regression models. In the first stage (PLCO) 41 SNPs clustered in 15 regions had p

  9. Building theories from case study research: the progressive case study

    NARCIS (Netherlands)

    Steenhuis, Harm-Jan; Bruijn, de Erik J.

    2006-01-01

    Meredith (1998) argues for more case and field research studies in the field of operations management. Based on a literature review, we discuss several existing approaches to case studies and their characteristics. These approaches include; the Grounded Theory approach which proposes no prior litera

  10. Progress in the synthesis and reactivity studies of metallabenzenes

    Institute of Scientific and Technical Information of China (English)

    HE Guomei; XIA Haiping; JIA Guocheng

    2004-01-01

    Metallabenzenes are metallacyclohexatriene complexes that are derived by replacement of one of the CH groups in benzene with a transition-metal fragment. Their synthesis and aromatic properties have recently attracted considerable attention. This paper summarizes the progress in the synthesis, aromatic property, and reactivity studies of metallabenzenes. We will describe the synthesis and reactivity of typical metallabenzenes with various metals (e.g. osmium, iridium, and ruthenium, etc.), the synthesis and structure of a recent reported example of metallanaphthalene and several rare examples of novel and stable metallabenzynes. Finally, the possible future developments in this field have also been suggested.

  11. Genome-wide association studies of obesity and metabolic syndrome.

    Science.gov (United States)

    Fall, Tove; Ingelsson, Erik

    2014-01-25

    Until just a few years ago, the genetic determinants of obesity and metabolic syndrome were largely unknown, with the exception of a few forms of monogenic extreme obesity. Since genome-wide association studies (GWAS) became available, large advances have been made. The first single nucleotide polymorphism robustly associated with increased body mass index (BMI) was in 2007 mapped to a gene with for the time unknown function. This gene, now known as fat mass and obesity associated (FTO) has been repeatedly replicated in several ethnicities and is affecting obesity by regulating appetite. Since the first report from a GWAS of obesity, an increasing number of markers have been shown to be associated with BMI, other measures of obesity or fat distribution and metabolic syndrome. This systematic review of obesity GWAS will summarize genome-wide significant findings for obesity and metabolic syndrome and briefly give a few suggestions of what is to be expected in the next few years. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  12. The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease.

    Science.gov (United States)

    Peng, Xinxia; Alföldi, Jessica; Gori, Kevin; Eisfeld, Amie J; Tyler, Scott R; Tisoncik-Go, Jennifer; Brawand, David; Law, G Lynn; Skunca, Nives; Hatta, Masato; Gasper, David J; Kelly, Sara M; Chang, Jean; Thomas, Matthew J; Johnson, Jeremy; Berlin, Aaron M; Lara, Marcia; Russell, Pamela; Swofford, Ross; Turner-Maier, Jason; Young, Sarah; Hourlier, Thibaut; Aken, Bronwen; Searle, Steve; Sun, Xingshen; Yi, Yaling; Suresh, M; Tumpey, Terrence M; Siepel, Adam; Wisely, Samantha M; Dessimoz, Christophe; Kawaoka, Yoshihiro; Birren, Bruce W; Lindblad-Toh, Kerstin; Di Palma, Federica; Engelhardt, John F; Palermo, Robert E; Katze, Michael G

    2014-12-01

    The domestic ferret (Mustela putorius furo) is an important animal model for multiple human respiratory diseases. It is considered the 'gold standard' for modeling human influenza virus infection and transmission. Here we describe the 2.41 Gb draft genome assembly of the domestic ferret, constituting 2.28 Gb of sequence plus gaps. We annotated 19,910 protein-coding genes on this assembly using RNA-seq data from 21 ferret tissues. We characterized the ferret host response to two influenza virus infections by RNA-seq analysis of 42 ferret samples from influenza time-course data and showed distinct signatures in ferret trachea and lung tissues specific to 1918 or 2009 human pandemic influenza virus infections. Using microarray data from 16 ferret samples reflecting cystic fibrosis disease progression, we showed that transcriptional changes in the CFTR-knockout ferret lung reflect pathways of early disease that cannot be readily studied in human infants with cystic fibrosis disease.

  13. Genome-Wide Association Study of Meiotic Recombination Phenotypes

    Science.gov (United States)

    Begum, Ferdouse; Chowdhury, Reshmi; Cheung, Vivian G.; Sherman, Stephanie L.; Feingold, Eleanor

    2016-01-01

    Meiotic recombination is an essential step in gametogenesis, and is one that also generates genetic diversity. Genome-wide association studies (GWAS) and molecular studies have identified genes that influence of human meiotic recombination. RNF212 is associated with total or average number of recombination events, and PRDM9 is associated with the locations of hotspots, or sequences where crossing over appears to cluster. In addition, a common inversion on chromosome 17 is strongly associated with recombination. Other genes have been identified by GWAS, but those results have not been replicated. In this study, using new datasets, we characterized additional recombination phenotypes to uncover novel candidates and further dissect the role of already known loci. We used three datasets totaling 1562 two-generation families, including 3108 parents with 4304 children. We estimated five different recombination phenotypes including two novel phenotypes (average recombination counts within recombination hotspots and outside of hotspots) using dense SNP array genotype data. We then performed gender-specific and combined-sex genome-wide association studies (GWAS) meta-analyses. We replicated associations for several previously reported recombination genes, including RNF212 and PRDM9. By looking specifically at recombination events outside of hotspots, we showed for the first time that PRDM9 has different effects in males and females. We identified several new candidate loci, particularly for recombination events outside of hotspots. These include regions near the genes SPINK6, EVC2, ARHGAP25, and DLGAP2. This study expands our understanding of human meiotic recombination by characterizing additional features that vary across individuals, and identifying regulatory variants influencing the numbers and locations of recombination events. PMID:27733454

  14. A genome-wide association study of optic disc parameters.

    Directory of Open Access Journals (Sweden)

    Wishal D Ramdas

    2010-06-01

    Full Text Available The optic nerve head is involved in many ophthalmic disorders, including common diseases such as myopia and open-angle glaucoma. Two of the most important parameters are the size of the optic disc area and the vertical cup-disc ratio (VCDR. Both are highly heritable but genetically largely undetermined. We performed a meta-analysis of genome-wide association (GWA data to identify genetic variants associated with optic disc area and VCDR. The gene discovery included 7,360 unrelated individuals from the population-based Rotterdam Study I and Rotterdam Study II cohorts. These cohorts revealed two genome-wide significant loci for optic disc area, rs1192415 on chromosome 1p22 (p = 6.72x10(-19 within 117 kb of the CDC7 gene and rs1900004 on chromosome 10q21.3-q22.1 (p = 2.67x10(-33 within 10 kb of the ATOH7 gene. They revealed two genome-wide significant loci for VCDR, rs1063192 on chromosome 9p21 (p = 6.15x10(-11 in the CDKN2B gene and rs10483727 on chromosome 14q22.3-q23 (p = 2.93x10(-10 within 40 kbp of the SIX1 gene. Findings were replicated in two independent Dutch cohorts (Rotterdam Study III and Erasmus Rucphen Family study; N = 3,612, and the TwinsUK cohort (N = 843. Meta-analysis with the replication cohorts confirmed the four loci and revealed a third locus at 16q12.1 associated with optic disc area, and four other loci at 11q13, 13q13, 17q23 (borderline significant, and 22q12.1 for VCDR. ATOH7 was also associated with VCDR independent of optic disc area. Three of the loci were marginally associated with open-angle glaucoma. The protein pathways in which the loci of optic disc area are involved overlap with those identified for VCDR, suggesting a common genetic origin.

  15. INTEGRATED GENOME-BASED STUDIES OF SHEWANELLA ECOPHYSIOLOGY

    Energy Technology Data Exchange (ETDEWEB)

    NEALSON, KENNETH H.

    2013-10-15

    This project had as its goals the understanding of the ecophysiology of the genus Shewanella using various genomics approaches. As opposed to other programs involving Shewanella, this one branched out into the various areas in which Shewanella cells are active, and included both basic and applied studies. All of the work was, to some extent, related to the ability of the bacteria to accomplish electron exchange between the cell and solid state electron acceptors and/or electron donors, a process we call Extracellular Electron Transport, or EET. The major accomplishments related to several different areas: Basic Science Studies: 1. Genetics and genomics of nitrate reduction, resulting in elucidation of atypical nitrate reduction systems in Shewanella oneidensis (MR-1)[2]. 2. Influence of bacterial strain and growth conditions on iron reduction, showing that rates of reduction, extents of reduction, and the formation of secondary minerals were different for different strains of Shewanella [3,4,9]. 3. Comparative genomics as a tool for comparing metabolic capacities of different Shewanella strains, and for predicting growth and metabolism [6,10,15]. In these studies, collaboration with ORNL, PNNL, and 4. Basic studies of electron transport in strain MR-1, both to poised electrodes, and via conductive nanowires [12,13]. This included the first accurate measurements of electrical energy generation by a single cell during electrode growth [12], and the demonstration of electrical conductivity along the length of bacterial nanowires [13]. 5. Impact of surface charge and electron flow on cell movement, cell attachment, cell growth, and biofilm formation [7.18]. The demonstration that interaction with solid state electron acceptors resulted in increased motility [7] led to the description of a phenomenon called electrokinesis. The importance of this for biofilm formation and for electron flow was hypothesized by Nealson & Finkel [18], and is now under study in several

  16. Genomic Aspects of Research Involving Polyploid Plants

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xiaohan [ORNL; Ye, Chuyu [ORNL; Tschaplinski, Timothy J [ORNL; Wullschleger, Stan D [ORNL; Tuskan, Gerald A [ORNL

    2011-01-01

    Almost all extant plant species have spontaneously doubled their genomes at least once in their evolutionary histories, resulting in polyploidy which provided a rich genomic resource for evolutionary processes. Moreover, superior polyploid clones have been created during the process of crop domestication. Polyploid plants generated by evolutionary processes and/or crop domestication have been the intentional or serendipitous focus of research dealing with the dynamics and consequences of genome evolution. One of the new trends in genomics research is to create synthetic polyploid plants which provide materials for studying the initial genomic changes/responses immediately after polyploid formation. Polyploid plants are also used in functional genomics research to study gene expression in a complex genomic background. In this review, we summarize the recent progress in genomics research involving ancient, young, and synthetic polyploid plants, with a focus on genome size evolution, genomics diversity, genomic rearrangement, genetic and epigenetic changes in duplicated genes, gene discovery, and comparative genomics. Implications on plant sciences including evolution, functional genomics, and plant breeding are presented. It is anticipated that polyploids will be a regular subject of genomics research in the foreseeable future as the rapid advances in DNA sequencing technology create unprecedented opportunities for discovering and monitoring genomic and transcriptomic changes in polyploid plants. The fast accumulation of knowledge on polyploid formation, maintenance, and divergence at whole-genome and subgenome levels will not only help plant biologists understand how plants have evolved and diversified, but also assist plant breeders in designing new strategies for crop improvement.

  17. Streptococcus thermophilus core genome: comparative genome hybridization study of 47 strains.

    Science.gov (United States)

    Rasmussen, Thomas Bovbjerg; Danielsen, Morten; Valina, Ondrej; Garrigues, Christel; Johansen, Eric; Pedersen, Martin Bastian

    2008-08-01

    A DNA microarray platform based on 2,200 genes from publicly available sequences was designed for Streptococcus thermophilus. We determined how single-nucleotide polymorphisms in the 65- to 75-mer oligonucleotide probe sequences affect the hybridization signals. The microarrays were then used for comparative genome hybridization (CGH) of 47 dairy S. thermophilus strains. An analysis of the exopolysaccharide genes in each strain confirmed previous findings that this class of genes is indeed highly variable. A phylogenetic tree based on the CGH data showed similar distances for most strains, indicating frequent recombination or gene transfer within S. thermophilus. By comparing genome sizes estimated from the microarrays and pulsed-field gel electrophoresis, the amount of unknown DNA in each strain was estimated. A core genome comprised of 1,271 genes detected in all 47 strains was identified. Likewise, a set of noncore genes detected in only some strains was identified. The concept of an industrial core genome is proposed. This is comprised of the genes in the core genome plus genes that are necessary in an applied industrial context.

  18. Research Progress in Genomic Imprinting in Mammals%哺乳动物基因组印记的研究进展

    Institute of Scientific and Technical Information of China (English)

    陈秀莉; 马利兵

    2015-01-01

    Genomic imprinting is a genetic phenomenon because of the different parents resulted from the allelic gene expression differences. The causes and the process of genomic imprinting is a hot issue of modern genetics. Mammals many genomic imprinting characteristic makes it become a focus biology problems in the post genome era. The evolution of genomic imprinting has played a special role in mammalian reproduction and development. This paper reviewed the characteristics of genomic imprinting、imprinting mechanism of gene imprinting, gene imprinting and the development of cloned animals, the research progress of the imprinting genes and the disease.%基因组印记是由亲本来源不同而导致等位基因表达差异的一种遗传现象。基因组印记产生的原因及过程是现代遗传学的一个热点问题。哺乳动物的许多基因组印记特征都使其成为后基因组时代的一个热点生物学问题。进化的基因组印记在哺乳动物生殖、发育中起到了特定的作用。综述了基因组印记的特点、印记基因的印记机理、基因印记与克隆动物的发育、印记基因与疾病的研究进展。

  19. Genome-wide association study of antisocial personality disorder

    Science.gov (United States)

    Rautiainen, M-R; Paunio, T; Repo-Tiihonen, E; Virkkunen, M; Ollila, H M; Sulkava, S; Jolanki, O; Palotie, A; Tiihonen, J

    2016-01-01

    The pathophysiology of antisocial personality disorder (ASPD) remains unclear. Although the most consistent biological finding is reduced grey matter volume in the frontal cortex, about 50% of the total liability to developing ASPD has been attributed to genetic factors. The contributing genes remain largely unknown. Therefore, we sought to study the genetic background of ASPD. We conducted a genome-wide association study (GWAS) and a replication analysis of Finnish criminal offenders fulfilling DSM-IV criteria for ASPD (N=370, N=5850 for controls, GWAS; N=173, N=3766 for controls and replication sample). The GWAS resulted in suggestive associations of two clusters of single-nucleotide polymorphisms at 6p21.2 and at 6p21.32 at the human leukocyte antigen (HLA) region. Imputation of HLA alleles revealed an independent association with DRB1*01:01 (odds ratio (OR)=2.19 (1.53–3.14), P=1.9 × 10-5). Two polymorphisms at 6p21.2 LINC00951–LRFN2 gene region were replicated in a separate data set, and rs4714329 reached genome-wide significance (OR=1.59 (1.37–1.85), P=1.6 × 10−9) in the meta-analysis. The risk allele also associated with antisocial features in the general population conditioned for severe problems in childhood family (β=0.68, P=0.012). Functional analysis in brain tissue in open access GTEx and Braineac databases revealed eQTL associations of rs4714329 with LINC00951 and LRFN2 in cerebellum. In humans, LINC00951 and LRFN2 are both expressed in the brain, especially in the frontal cortex, which is intriguing considering the role of the frontal cortex in behavior and the neuroanatomical findings of reduced gray matter volume in ASPD. To our knowledge, this is the first study showing genome-wide significant and replicable findings on genetic variants associated with any personality disorder. PMID:27598967

  20. A whole-genome association study for pig reproductive traits.

    Science.gov (United States)

    Onteru, S K; Fan, B; Du, Z-Q; Garrick, D J; Stalder, K J; Rothschild, M F

    2012-02-01

    A whole-genome association study was performed for reproductive traits in commercial sows using the PorcineSNP60 BeadChip and Bayesian statistical methods. The traits included total number born (TNB), number born alive (NBA), number of stillborn (SB), number of mummified foetuses at birth (MUM) and gestation length (GL) in each of the first three parities. We report the associations of informative QTL and the genes within the QTL for each reproductive trait in different parities. These results provide evidence of gene effects having temporal impacts on reproductive traits in different parities. Many QTL identified in this study are new for pig reproductive traits. Around 48% of total genes located in the identified QTL regions were predicted to be involved in placental functions. The genomic regions containing genes important for foetal developmental (e.g. MEF2C) and uterine functions (e.g. PLSCR4) were associated with TNB and NBA in the first two parities. Similarly, QTL in other foetal developmental (e.g. HNRNPD and AHR) and placental (e.g. RELL1 and CD96) genes were associated with SB and MUM in different parities. The QTL with genes related to utero-placental blood flow (e.g. VEGFA) and hematopoiesis (e.g. MAFB) were associated with GL differences among sows in this population. Pathway analyses using genes within QTL identified some modest underlying biological pathways, which are interesting candidates (e.g. the nucleotide metabolism pathway for SB) for pig reproductive traits in different parities. Further validation studies on large populations are warranted to improve our understanding of the complex genetic architecture for pig reproductive traits.

  1. 猪链球菌的比较基因组学研究进展%Progress on research of comparative genomics of Streptococcus suis

    Institute of Scientific and Technical Information of China (English)

    郑霄

    2011-01-01

    Streptococcus suis is an important zoonotic agent and could cause outbreaks of the infections among pigs and humans. Over the past five years, great progress had been achieved in the field of S. suis genomics. By now six S. suis genomes have been sequenced and publicly available. Furthermore, the application of new comparative genomics technologies on such genomes had led to the identification of new pathogenicity islands and pathogenesis-related genes,which greatly boosted the research on pathogenic mechanisms of S. suis.%猪链球菌是一种重要的人兽共患病病原菌,可以引起人猪链球菌病暴发流行.近几年来,猪链球菌的基因组学研究发展迅速:共有6株猪链球菌的基因组全序列公布;采用多种比较基因组技术发现了高致病性猪链球菌相关的毒力岛和特异基因,为研究猪链球菌的致病机制提供了重要线索.

  2. Progress on Functional Genomics of Some Important Zoonotic Parasites%重要人兽共患寄生虫功能基因组学研究进展

    Institute of Scientific and Technical Information of China (English)

    艾琳; 陈韶红; 陈家旭

    2011-01-01

    随着分子生物学技术的迅速发展,基因组学的研究已从结构基因组学转向功能基因组学,对于基因功能的研究也由单一基因转向大规模、批量分析.为促进我国寄生虫功能基因组学的研究,本文介绍几种重要的功能基因组学研究技术方法,并对近几年来一些重要寄生虫功能基因组学的最新研究进展作一综述.%With the development of molecular biology, genomics research has been expanded from structural genomics to functional genomics, and from single gene to massive batch. This paper summarizes the progress of structural genomics of some zoonotic parasites and major technical methods.

  3. The human genome project: Information management, access, and regulation. Technical progress report, 1 April--31 August 1993

    Energy Technology Data Exchange (ETDEWEB)

    McInerney, J.D.; Micikas, L.B.

    1993-09-10

    Efforts are described to prepare educational materials including computer based as well as conventional type teaching materials for training interested high school and elementary students in aspects of Human Genome Project.

  4. Importance of genomic studies for drug withdrawal with mental toxicities

    Directory of Open Access Journals (Sweden)

    Da Yong Lu

    2011-09-01

    Full Text Available Undesired side-effects and toxicities of drugs, especially in the area of new-drug development, are negligibleless, unpredicable and often disastrous once being encountered. The suicidal behavior caused by antidepressant treatment is a typical of clinical evidence recently being discovered. We previously hypothesized that patients’ genetic status would decide the suicidal incident rate of antidepressants - it is pharmacogenetics of antidepressants may contribute of this toxicity in patients. In this review, we discuss this problem by comparing many strings of pharmacogenomics evidence of antidepressants recently being published with many other strings of evidence such as drug withdrawal with hepatotoxicity. We argue herein that pharmacogenetics may be very useful in drug withdrawal for mental toxicity. Because this is low-incidence toxicities, which are more reliable on human’s genetic characteristics. We stress the importance of genomics studies for drug withdrawal in future.

  5. Life Sciences Division and Center for Human Genome Studies 1994

    Energy Technology Data Exchange (ETDEWEB)

    Cram, L.S.; Stafford, C. [comp.

    1995-09-01

    This report summarizes the research and development activities of the Los Alamos National Laboratory`s Life Sciences Division and the biological aspects of the Center for Human Genome Studies for the calendar year 1994. The technical portion of the report is divided into two parts, (1) selected research highlights and (2) research projects and accomplishments. The research highlights provide a more detailed description of a select set of projects. A technical description of all projects is presented in sufficient detail so that the informed reader will be able to assess the scope and significance of each project. Summaries useful to the casual reader desiring general information have been prepared by the group leaders and appear in each group overview. Investigators on the staff of the Life Sciences Division will be pleased to provide further information.

  6. Genome-Wide Association Study of Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Naomi Ogawa

    2010-01-01

    Full Text Available Coronary artery disease (CAD is a multifactorial disease with environmental and genetic determinants. The genetic determinants of CAD have previously been explored by the candidate gene approach. Recently, the data from the International HapMap Project and the development of dense genotyping chips have enabled us to perform genome-wide association studies (GWAS on a large number of subjects without bias towards any particular candidate genes. In 2007, three chip-based GWAS simultaneously revealed the significant association between common variants on chromosome 9p21 and CAD. This association was replicated among other ethnic groups and also in a meta-analysis. Further investigations have detected several other candidate loci associated with CAD. The chip-based GWAS approach has identified novel and unbiased genetic determinants of CAD and these insights provide the important direction to better understand the pathogenesis of CAD and to develop new and improved preventive measures and treatments for CAD.

  7. progress and prospects for studies on chinese amphibians

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    this work summarizes the history and progress of the studies on chinese amphibians since they first appeared in the chinese literature.a wide range of research has been carried out,including the history of the definition of amphibians,faunal surveys,systematic research,ecological research,biochemical research (isozyme and other proteins or peptides,chromosomes,dna),anatomical research,embryological research,phylogenetic and zoogeographical research,and many others such as ultrastructure of organs,crossbreeding test,regeneration of organs,abnormality survey,acoustics,fossils,sperm ultrastructure and parasites.in addition,the prospects for studies on chinese amphibians in future are proposed in this paper.

  8. Integrative computational approach for genome-based study of microbial lipid-degrading enzymes.

    Science.gov (United States)

    Vorapreeda, Tayvich; Thammarongtham, Chinae; Laoteng, Kobkul

    2016-07-01

    Lipid-degrading or lipolytic enzymes have gained enormous attention in academic and industrial sectors. Several efforts are underway to discover new lipase enzymes from a variety of microorganisms with particular catalytic properties to be used for extensive applications. In addition, various tools and strategies have been implemented to unravel the functional relevance of the versatile lipid-degrading enzymes for special purposes. This review highlights the study of microbial lipid-degrading enzymes through an integrative computational approach. The identification of putative lipase genes from microbial genomes and metagenomic libraries using homology-based mining is discussed, with an emphasis on sequence analysis of conserved motifs and enzyme topology. Molecular modelling of three-dimensional structure on the basis of sequence similarity is shown to be a potential approach for exploring the structural and functional relationships of candidate lipase enzymes. The perspectives on a discriminative framework of cutting-edge tools and technologies, including bioinformatics, computational biology, functional genomics and functional proteomics, intended to facilitate rapid progress in understanding lipolysis mechanism and to discover novel lipid-degrading enzymes of microorganisms are discussed.

  9. A genome-wide methylation study on obesity

    Science.gov (United States)

    Xu, Xiaojing; Su, Shaoyong; Barnes, Vernon A.; De Miguel, Carmen; Pollock, Jennifer; Ownby, Dennis; Shi, Huidong; Zhu, Haidong; Snieder, Harold; Wang, Xiaoling

    2013-01-01

    Besides differential methylation, DNA methylation variation has recently been proposed and demonstrated to be a potential contributing factor to cancer risk. Here we aim to examine whether differential variability in methylation is also an important feature of obesity, a typical non-malignant common complex disease. We analyzed genome-wide methylation profiles of over 470,000 CpGs in peripheral blood samples from 48 obese and 48 lean African-American youth aged 14–20 y old. A substantial number of differentially variable CpG sites (DVCs), using statistics based on variances, as well as a substantial number of differentially methylated CpG sites (DMCs), using statistics based on means, were identified. Similar to the findings in cancers, DVCs generally exhibited an outlier structure and were more variable in cases than in controls. By randomly splitting the current sample into a discovery and validation set, we observed that both the DVCs and DMCs identified from the first set could independently predict obesity status in the second set. Furthermore, both the genes harboring DMCs and the genes harboring DVCs showed significant enrichment of genes identified by genome-wide association studies on obesity and related diseases, such as hypertension, dyslipidemia, type 2 diabetes and certain types of cancers, supporting their roles in the etiology and pathogenesis of obesity. We generalized the recent finding on methylation variability in cancer research to obesity and demonstrated that differential variability is also an important feature of obesity-related methylation changes. Future studies on the epigenetics of obesity will benefit from both statistics based on means and statistics based on variances. PMID:23644594

  10. A genome-wide association study of anorexia nervosa

    Science.gov (United States)

    Boraska, Vesna; Franklin, Christopher S; Floyd, James AB; Thornton, Laura M; Huckins, Laura M; Southam, Lorraine; Rayner, N William; Tachmazidou, Ioanna; Klump, Kelly L; Treasure, Janet; Lewis, Cathryn M; Schmidt, Ulrike; Tozzi, Federica; Kiezebrink, Kirsty; Hebebrand, Johannes; Gorwood, Philip; Adan, Roger AH; Kas, Martien JH; Favaro, Angela; Santonastaso, Paolo; Fernández-Aranda, Fernando; Gratacos, Monica; Rybakowski, Filip; Dmitrzak-Weglarz, Monika; Kaprio, Jaakko; Keski-Rahkonen, Anna; Raevuori, Anu; Van Furth, Eric F; Landt, Margarita CT Slof-Op t; Hudson, James I; Reichborn-Kjennerud, Ted; Knudsen, Gun Peggy S; Monteleone, Palmiero; Kaplan, Allan S; Karwautz, Andreas; Hakonarson, Hakon; Berrettini, Wade H; Guo, Yiran; Li, Dong; Schork, Nicholas J.; Komaki, Gen; Ando, Tetsuya; Inoko, Hidetoshi; Esko, Tõnu; Fischer, Krista; Männik, Katrin; Metspalu, Andres; Baker, Jessica H; Cone, Roger D; Dackor, Jennifer; DeSocio, Janiece E; Hilliard, Christopher E; O'Toole, Julie K; Pantel, Jacques; Szatkiewicz, Jin P; Taico, Chrysecolla; Zerwas, Stephanie; Trace, Sara E; Davis, Oliver SP; Helder, Sietske; Bühren, Katharina; Burghardt, Roland; de Zwaan, Martina; Egberts, Karin; Ehrlich, Stefan; Herpertz-Dahlmann, Beate; Herzog, Wolfgang; Imgart, Hartmut; Scherag, André; Scherag, Susann; Zipfel, Stephan; Boni, Claudette; Ramoz, Nicolas; Versini, Audrey; Brandys, Marek K; Danner, Unna N; de Kovel, Carolien; Hendriks, Judith; Koeleman, Bobby PC; Ophoff, Roel A; Strengman, Eric; van Elburg, Annemarie A; Bruson, Alice; Clementi, Maurizio; Degortes, Daniela; Forzan, Monica; Tenconi, Elena; Docampo, Elisa; Escaramís, Geòrgia; Jiménez-Murcia, Susana; Lissowska, Jolanta; Rajewski, Andrzej; Szeszenia-Dabrowska, Neonila; Slopien, Agnieszka; Hauser, Joanna; Karhunen, Leila; Meulenbelt, Ingrid; Slagboom, P Eline; Tortorella, Alfonso; Maj, Mario; Dedoussis, George; Dikeos, Dimitris; Gonidakis, Fragiskos; Tziouvas, Konstantinos; Tsitsika, Artemis; Papezova, Hana; Slachtova, Lenka; Martaskova, Debora; Kennedy, James L.; Levitan, Robert D.; Yilmaz, Zeynep; Huemer, Julia; Koubek, Doris; Merl, Elisabeth; Wagner, Gudrun; Lichtenstein, Paul; Breen, Gerome; Cohen-Woods, Sarah; Farmer, Anne; McGuffin, Peter; Cichon, Sven; Giegling, Ina; Herms, Stefan; Rujescu, Dan; Schreiber, Stefan; Wichmann, H-Erich; Dina, Christian; Sladek, Rob; Gambaro, Giovanni; Soranzo, Nicole; Julia, Antonio; Marsal, Sara; Rabionet, Raquel; Gaborieau, Valerie; Dick, Danielle M; Palotie, Aarno; Ripatti, Samuli; Widén, Elisabeth; Andreassen, Ole A; Espeseth, Thomas; Lundervold, Astri; Reinvang, Ivar; Steen, Vidar M; Le Hellard, Stephanie; Mattingsdal, Morten; Ntalla, Ioanna; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Navratilova, Marie; Gallinger, Steven; Pinto, Dalila; Scherer, Stephen; Aschauer, Harald; Carlberg, Laura; Schosser, Alexandra; Alfredsson, Lars; Ding, Bo; Klareskog, Lars; Padyukov, Leonid; Finan, Chris; Kalsi, Gursharan; Roberts, Marion; Logan, Darren W; Peltonen, Leena; Ritchie, Graham RS; Barrett, Jeffrey C; Estivill, Xavier; Hinney, Anke; Sullivan, Patrick F; Collier, David A; Zeggini, Eleftheria; Bulik, Cynthia M

    2015-01-01

    Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01×10-7) in SOX2OT and rs17030795 (P=5.84×10-6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76×10-6) between CUL3 and FAM124B and rs1886797 (P=8.05×10-6) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4×10-6), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field. PMID:24514567

  11. A genome-wide association study of anorexia nervosa.

    Science.gov (United States)

    Boraska, V; Franklin, C S; Floyd, J A B; Thornton, L M; Huckins, L M; Southam, L; Rayner, N W; Tachmazidou, I; Klump, K L; Treasure, J; Lewis, C M; Schmidt, U; Tozzi, F; Kiezebrink, K; Hebebrand, J; Gorwood, P; Adan, R A H; Kas, M J H; Favaro, A; Santonastaso, P; Fernández-Aranda, F; Gratacos, M; Rybakowski, F; Dmitrzak-Weglarz, M; Kaprio, J; Keski-Rahkonen, A; Raevuori, A; Van Furth, E F; Slof-Op 't Landt, M C T; Hudson, J I; Reichborn-Kjennerud, T; Knudsen, G P S; Monteleone, P; Kaplan, A S; Karwautz, A; Hakonarson, H; Berrettini, W H; Guo, Y; Li, D; Schork, N J; Komaki, G; Ando, T; Inoko, H; Esko, T; Fischer, K; Männik, K; Metspalu, A; Baker, J H; Cone, R D; Dackor, J; DeSocio, J E; Hilliard, C E; O'Toole, J K; Pantel, J; Szatkiewicz, J P; Taico, C; Zerwas, S; Trace, S E; Davis, O S P; Helder, S; Bühren, K; Burghardt, R; de Zwaan, M; Egberts, K; Ehrlich, S; Herpertz-Dahlmann, B; Herzog, W; Imgart, H; Scherag, A; Scherag, S; Zipfel, S; Boni, C; Ramoz, N; Versini, A; Brandys, M K; Danner, U N; de Kovel, C; Hendriks, J; Koeleman, B P C; Ophoff, R A; Strengman, E; van Elburg, A A; Bruson, A; Clementi, M; Degortes, D; Forzan, M; Tenconi, E; Docampo, E; Escaramís, G; Jiménez-Murcia, S; Lissowska, J; Rajewski, A; Szeszenia-Dabrowska, N; Slopien, A; Hauser, J; Karhunen, L; Meulenbelt, I; Slagboom, P E; Tortorella, A; Maj, M; Dedoussis, G; Dikeos, D; Gonidakis, F; Tziouvas, K; Tsitsika, A; Papezova, H; Slachtova, L; Martaskova, D; Kennedy, J L; Levitan, R D; Yilmaz, Z; Huemer, J; Koubek, D; Merl, E; Wagner, G; Lichtenstein, P; Breen, G; Cohen-Woods, S; Farmer, A; McGuffin, P; Cichon, S; Giegling, I; Herms, S; Rujescu, D; Schreiber, S; Wichmann, H-E; Dina, C; Sladek, R; Gambaro, G; Soranzo, N; Julia, A; Marsal, S; Rabionet, R; Gaborieau, V; Dick, D M; Palotie, A; Ripatti, S; Widén, E; Andreassen, O A; Espeseth, T; Lundervold, A; Reinvang, I; Steen, V M; Le Hellard, S; Mattingsdal, M; Ntalla, I; Bencko, V; Foretova, L; Janout, V; Navratilova, M; Gallinger, S; Pinto, D; Scherer, S W; Aschauer, H; Carlberg, L; Schosser, A; Alfredsson, L; Ding, B; Klareskog, L; Padyukov, L; Courtet, P; Guillaume, S; Jaussent, I; Finan, C; Kalsi, G; Roberts, M; Logan, D W; Peltonen, L; Ritchie, G R S; Barrett, J C; Estivill, X; Hinney, A; Sullivan, P F; Collier, D A; Zeggini, E; Bulik, C M

    2014-10-01

    Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

  12. Progresses in research on the functional genomics on Tribolium castaneum%赤拟谷盗功能基因组学研究进展

    Institute of Scientific and Technical Information of China (English)

    李承军; 王艳允; 刘幸; 桑明; 李斌

    2011-01-01

    赤拟谷盗Tribolium castaneum是一种重要的模式生物,在遗传、发育、生化与免疫等研究领域均取得了重要的研究进展.同时它也是一种危害极大的鞘翅目类储粮害虫,在世界各地都有分布,每年给储藏物造成了数十亿美元的经济损失.其全基因组测序的完成、遗传操作体系的构建及系统RNAi方法的应用都极大地促进了其功能基因组学的研究.本文综述了近年来赤拟谷盗基因组计划及功能基因组学的研究进展,拟为赤拟谷盗的生物学研究和防治奠定基础.%Tribolium castaneum is a powerful model organism for research in such fields as insect genetics, biology development, biochemistry and immunity, and rapid and useful progress has been made in these fields in recent years. T. Castaneum is also an important coleopteran pest of stored agricultural products. This globally distributed pest causes billions of dollars of damage to such stored products each year. Recently, the sequencing of the entire genome of T. Castaneum, the construction of their genetics operation systems, and the utilization of the systemic RNA interference, have greatly facilitated and accelerated research on their functional genomics and the related fields. In order to facilitate research on both the fundamental biology and control of T. Castaneum, we here review progresses and achievements in research on T. Castaneum genome projects and functional genomics over the past few years.

  13. Enhancing genomic prediction with genome-wide association studies in multiparental maize populations

    Science.gov (United States)

    Genome-wide association mapping using dense marker sets has identified some nucleotide variants affecting complex traits which have been validated with fine-mapping and functional analysis. Many sequence variants associated with complex traits in maize have small effects and low repeatability, howev...

  14. Genomic MRI - a Public Resource for Studying Sequence Patterns within Genomic DNA

    Science.gov (United States)

    Prakash, Ashwin; Bechtel, Jason; Fedorov, Alexei

    2011-01-01

    Non-coding genomic regions in complex eukaryotes, including intergenic areas, introns, and untranslated segments of exons, are profoundly non-random in their nucleotide composition and consist of a complex mosaic of sequence patterns. These patterns include so-called Mid-Range Inhomogeneity (MRI) regions -- sequences 30-10000 nucleotides in length that are enriched by a particular base or combination of bases (e.g. (G+T)-rich, purine-rich, etc.). MRI regions are associated with unusual (non-B-form) DNA structures that are often involved in regulation of gene expression, recombination, and other genetic processes (Fedorova & Fedorov 2010). The existence of a strong fixation bias within MRI regions against mutations that tend to reduce their sequence inhomogeneity additionally supports the functionality and importance of these genomic sequences (Prakash et al. 2009). Here we demonstrate a freely available Internet resource -- the Genomic MRI program package -- designed for computational analysis of genomic sequences in order to find and characterize various MRI patterns within them (Bechtel et al. 2008). This package also allows generation of randomized sequences with various properties and level of correspondence to the natural input DNA sequences. The main goal of this resource is to facilitate examination of vast regions of non-coding DNA that are still scarcely investigated and await thorough exploration and recognition. PMID:21610667

  15. Progression from Sustained BK Viruria to Sustained BK Viremia with Immunosuppression Reduction Is Not Associated with Changes in the Noncoding Control Region of the BK Virus Genome

    Directory of Open Access Journals (Sweden)

    Imran A. Memon

    2012-01-01

    We performed PCR amplification and sequencing of (1 stored urine and (2 plasma samples from the time of peak viremia from 11 patients with sustained viremia who participated in a 200-patient clinical trial. The antimetabolite was withdrawn for BK viremia and reduction of the calcineurin inhibitor for sustained BK viremia. DNA sequencing from the 11 patients with sustained viremia revealed 8 insertions, 16 transversions, 3 deletions, and 17 transitions. None were deemed significant. No patient developed clinically evident BKVAN. Our data support, at a genomic level, the effectiveness of reduction of immunosuppression for prevention of progression from viremia to BKVAN.

  16. Study Progress and Trends of Strategic Environmental Assessment in China

    Institute of Scientific and Technical Information of China (English)

    Cai Chunmiao; Shang Jincheng

    2009-01-01

    Strategic environmental assessment (SEA) in China has developed rapidly since it was introduced into China in the 1990s.Chinese government promulgated the Environmental Impact As-sessment Law of China (hereinafter referred to as the EIA Law) in 2002.In this law, it is stipulated clearly that regional and sector plans should be assessed.Through investigating materials and ana-lyzing literatures, this article analyses the practical and academic study achievements of SEA in China that have been achieved since the EIA Law was implemented, probes into the current situation of the main level of SEA in China--plan EIA, then summarizes the development characteristics, and eventually, puts forward the development trends of SEA in China.The research conclusions can offer the foundations for comprehending systematically the progress of SEA in China.

  17. Genome size and sequence composition of moso bamboo: A comparative study

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Moso bamboo (Phyllostachys pubescens) is one of the world's most important bamboo species. It has the largest area of all planted bamboo―over two-thirds of the total bamboo forest area―and the highest economic value in China. Moso bamboo is a tetraploid (4x=48) and a special member of the grasses family. Although several genomes have been sequenced or are being sequenced in the grasses family, we know little about the genome of the bambusoids (bamboos). In this study, the moso bamboo genome size was estimated to be about 2034 Mb by flow cytometry (FCM), using maize (cv. B73) and rice (cv. Nipponbare) as internal references. The rice genome has been sequenced and the maize genome is being sequenced. We found that the size of the moso bamboo genome was similar to that of maize but significantly larger than that of rice. To determine whether the bamboo genome had a high proportion of repeat elements, similar to that of the maize genome, approximately 1000 genome survey sequences (GSS) were generated. Sequence analysis showed that the proportion of repeat elements was 23.3% for the bamboo genome, which is significantly lower than that of the maize genome (65.7%). The bamboo repeat elements were mainly Gypsy/DIRS1 and Ty1/Copia LTR retrotransposons (14.7%), with a few DNA transposons. However, more genomic sequences are needed to confirm the above results due to several factors, such as the limitation of our GSS data. This study is the first to investigate sequence composition of the bamboo genome. Our results are valuable for future genome research of moso and other bamboos.

  18. Genetic Studies of Quantitative MCI and AD Phenotypes in ADNI: Progress, Opportunities, and Plans

    Science.gov (United States)

    Saykin, Andrew J.; Shen, Li; Yao, Xiaohui; Kim, Sungeun; Nho, Kwangsik; Risacher, Shannon L.; Ramanan, Vijay K.; Foroud, Tatiana M.; Faber, Kelly M.; Sarwar, Nadeem; Munsie, Leanne M.; Hu, Xiaolan; Soares, Holly D.; Potkin, Steven G.; Thompson, Paul M.; Kauwe, John S.K.; Kaddurah-Daouk, Rima; Green, Robert C.; Toga, Arthur W.; Weiner, Michael W.

    2015-01-01

    INTRODUCTION Genetic data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) has been crucial in advancing the understanding of AD pathophysiology. Here we provide an update on sample collection, scientific progress and opportunities, conceptual issues, and future plans. METHODS Lymphoblastoid cell lines and DNA and RNA samples from blood have been collected and banked, and data and biosamples have been widely disseminated. To date, APOE genotyping, genome-wide association study (GWAS), and whole exome and whole genome sequencing (WES, WGS) data have been obtained and disseminated. RESULTS ADNI genetic data have been downloaded thousands of times and over 300 publications have resulted, including reports of large scale GWAS by consortia to which ADNI contributed. Many of the first applications of quantitative endophenotype association studies employed ADNI data, including some of the earliest GWAS and pathway-based studies of biospecimen and imaging biomarkers, as well as memory and other clinical/cognitive variables. Other contributions include some of the first WES and WGS data sets and reports in healthy controls, MCI, and AD. DISCUSSION Numerous genetic susceptibility and protective markers for AD and disease biomarkers have been identified and replicated using ADNI data, and have heavily implicated immune, mitochondrial, cell cycle/fate, and other biological processes. Early sequencing studies suggest that rare and structural variants are likely to account for significant additional phenotypic variation. Longitudinal analyses of transcriptomic, proteomic, metabolomic, and epigenomic changes will also further elucidate dynamic processes underlying preclinical and prodromal stages of disease. Integration of this unique collection of multi-omics data within a systems biology framework will help to separate truly informative markers of early disease mechanisms and potential novel therapeutic targets from the vast background of less relevant biological

  19. Genome-Wide Association Study of Serum Selenium Concentrations

    Directory of Open Access Journals (Sweden)

    Ulrike Peters

    2013-05-01

    Full Text Available Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this hypothesis. Therefore, we conducted a two-stage genome-wide association study to identify genetic variants associated with serum selenium concentrations in 1203 European descents from two cohorts: the Prostate, Lung, Colorectal, and Ovarian (PLCO Cancer Screening and the Women’s Health Initiative (WHI. We tested association between 2,474,333 single nucleotide polymorphisms (SNPs and serum selenium concentrations using linear regression models. In the first stage (PLCO 41 SNPs clustered in 15 regions had p < 1 × 10−5. None of these 41 SNPs reached the significant threshold (p = 0.05/15 regions = 0.003 in the second stage (WHI. Three SNPs had p < 0.05 in the second stage (rs1395479 and rs1506807 in 4q34.3/AGA-NEIL3; and rs891684 in 17q24.3/SLC39A11 and had p between 2.62 × 10−7 and 4.04 × 10−7 in the combined analysis (PLCO + WHI. Additional studies are needed to replicate these findings. Identification of genetic variation that impacts selenium concentrations may contribute to a better understanding of which genes regulate circulating selenium concentrations.

  20. Genome-wide association study of circulating retinol levels.

    Science.gov (United States)

    Mondul, Alison M; Yu, Kai; Wheeler, William; Zhang, Hong; Weinstein, Stephanie J; Major, Jacqueline M; Cornelis, Marilyn C; Männistö, Satu; Hazra, Aditi; Hsing, Ann W; Jacobs, Kevin B; Eliassen, Heather; Tanaka, Toshiko; Reding, Douglas J; Hendrickson, Sara; Ferrucci, Luigi; Virtamo, Jarmo; Hunter, David J; Chanock, Stephen J; Kraft, Peter; Albanes, Demetrius

    2011-12-01

    Retinol is one of the most biologically active forms of vitamin A and is hypothesized to influence a wide range of human diseases including asthma, cardiovascular disease, infectious diseases and cancer. We conducted a genome-wide association study of 5006 Caucasian individuals drawn from two cohorts of men: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. We identified two independent single-nucleotide polymorphisms associated with circulating retinol levels, which are located near the transthyretin (TTR) and retinol binding protein 4 (RBP4) genes which encode major carrier proteins of retinol: rs1667255 (P =2.30× 10(-17)) and rs10882272 (P =6.04× 10(-12)). We replicated the association with rs10882272 in RBP4 in independent samples from the Nurses' Health Study and the Invecchiare in Chianti Study (InCHIANTI) that included 3792 women and 504 men (P =9.49× 10(-5)), but found no association for retinol with rs1667255 in TTR among women, thus suggesting evidence for gender dimorphism (P-interaction=1.31× 10(-5)). Discovery of common genetic variants associated with serum retinol levels may provide further insight into the contribution of retinol and other vitamin A compounds to the development of cancer and other complex diseases.

  1. Molecular studies of functional aspects of plant mitochondria. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Siedow, J.N.

    1992-03-03

    The goal of this research is to characterize the mechanism by which a protein encoded by mitochondrial genome of cms-T maize (URF13) interacts with a family of the compounds produced by certain fungi (T-toxins) to permeabilize biological membranes. The research carried out during the current funding period has focused on the structure of URF13, and the results support the validity of the three-helix model of URF13 and provide direct evidence for the oligomeric nature of at least some of the URF13 molecules in the membrane. In addition, the toxin binding studies have provided insight into the dynamic nature of the T-toxin:URF13 interaction and the extent to which Asp-39 is crucial to the interaction that leads to membrane pore formation. Additional knowledge of the structure of URF13 is needed if the nature of the interaction between URF13 and T-toxin to produce a hydrophilic pore within the membrane is to ultimately be understood.

  2. Functional Genomics of Wood Quality and Properties

    Institute of Scientific and Technical Information of China (English)

    Wei Tang; Xiaoyan Luo; Aaron Nelson; Hilary Collver; Katherine Kinken

    2003-01-01

    Genomics promises to enrich the investigations of biology and biochemistry. Current advancements in genomics have major implications for genetic improvement in animals, plants, and microorganisms, and for our understanding of cell growth, development, differentiation, and communication. Significant progress has been made in the understanding of plant genomics in recent years, and the area continues to progress rapidly. Functional genomics offers enormous potential to tree improvement and the understanding of gene expression in this area of science worldwide.In this review we focus on functional genomics of wood quality and properties in trees, mainly based on progresses made in genomics study of Pinus and Populus.The aims of this review are to summarize the current status of functional genomics including: (1) Gene discovery; (2) EST and genomic sequencing; (3) From EST to functional genomics; (4) Approaches to functional analysis; (5) Engineering lignin biosynthesis; (6) Modification of cell wall biogenesis; and (7) Molecular modelling.Functional genomics has been greatly invested worldwide and will be important in identifying candidate genes whose function is critical to all aspects of plant growth, development, differentiation, and defense. Forest biotechnology industry will significantly benefit from the advent of functional genomics of wood quality and properties.

  3. Theoretical studies in nuclear reactions and nuclear structure. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    1992-05-01

    Research in the Maryland Nuclear Theory Group focusses on problems in four basic areas of current relevance. Hadrons in nuclear matter; the structure of hadrons; relativistic nuclear physics and heavy ion dynamics and related processes. The section on hadrons in nuclear matter groups together research items which are aimed at exploring ways in which the properties of nucleons and the mesons which play a role in the nuclear force are modified in the nuclear medium. A very interesting result has been the finding that QCD sum rules supply a new insight into the decrease of the nucleon`s mass in the nuclear medium. The quark condensate, which characterizes spontaneous chiral symmetry breaking of the late QCD vacuum, decreases in nuclear matter and this is responsible for the decrease of the nucleon`s mass. The section on the structure of hadrons contains progress reports on our research aimed at understanding the structure of the nucleon. Widely different approaches are being studied, e.g., lattice gauge calculations, QCD sum rules, quark-meson models with confinement and other hedgehog models. A major goal of this type of research is to develop appropriate links between nuclear physics and QCD. The section on relativistic nuclear physics represents our continuing interest in developing an appropriate relativistic framework for nuclear dynamics. A Lorentz-invariant description of the nuclear force suggests a similar decrease of the nucleon`s mass in the nuclear medium as has been found from QCD sum rules. Work in progress extends previous successes in elastic scattering to inelastic scattering of protons by nuclei. The section on heavy ion dynamics and related processes reports on research into the e{sup +}e{sup {minus}} problem and heavy ion dynamics.

  4. Speech Therapy in Primary Progressive Aphasia: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Luísa Farrajota

    2012-08-01

    Full Text Available Background: Primary progressive aphasia (PPA is a neurodegenerative disorder with no effective pharmacological treatment. Cognition-based interventions are adequate alternatives, but their benefit has not been thoroughly explored. Our aim was to study the effect of speech and language therapy (SLT on naming ability in PPA. Methods: An open parallel prospective longitudinal study involving two centers was designed to compare patients with PPA submitted to SLT (1 h/week for 11 months with patients receiving no therapy. Twenty patients were enrolled and undertook baseline language and neuropsychological assessments; among them, 10 received SLT and 10 constituted an age- and education-matched historical control group. The primary outcome measure was the change in group mean performance on the Snodgrass and Vanderwart naming test between baseline and follow-up assessments. Results: Intervention and control groups did not significantly differ on demographic and clinical variables at baseline. A mixed repeated measures ANOVA revealed a significant main effect of therapy (F(1,18 = 10.763; p = 0.005 on the performance on the Snodgrass and Vanderwart naming test. Conclusion: Although limited by a non-randomized open study design with a historical control group, the present study suggests that SLT may have a benefit in PPA, and it should prompt a randomized, controlled, rater-blind clinical trial.

  5. The Progression and Early detection of Subclinical Atherosclerosis (PESA) study

    DEFF Research Database (Denmark)

    Fernández-Ortiz, Antonio; Jiménez-Borreguero, L Jesús; Peñalvo, José L

    2013-01-01

    The presence of subclinical atherosclerosis is a likely predictor of cardiovascular events; however, factors associated with the early stages and progression of atherosclerosis are poorly defined.......The presence of subclinical atherosclerosis is a likely predictor of cardiovascular events; however, factors associated with the early stages and progression of atherosclerosis are poorly defined....

  6. Epidemiological studies of esophageal cancer in the era of genome-wide association studies

    Institute of Scientific and Technical Information of China (English)

    An-Hui; Wang; Yuan; Liu; Bo; Wang; Yi-Xuan; He; Ye-Xian; Fang; Yong-Ping; Yan

    2014-01-01

    Esophageal cancer(EC) caused about 395000 deaths in 2010. China has the most cases of EC and EC is the fourth leading cause of cancer death in China. Esophageal squamous cell carcinoma(ESCC) is the predominant histologic type(90%-95%), while the incidence of esophageal adenocarcinoma(EAC) remains extremely low in China. Traditional epidemiological studies have revealed that environmental carcinogens are risk factors for EC. Molecular epidemiological studies revealed that susceptibility to EC is influenced by both environmental and genetic risk factors. Of all the risk factors for EC, some are associated with the risk of ESCC and others with the risk of EAC. However, the details and mechanisms of risk factors involved in the process for EC are unclear. The advanced methods and techniques used in human genome studies bring a great opportunity for researchers to explore and identify the details of those risk factors or susceptibility genes involved inthe process of EC. Human genome epidemiology is a new branch of epidemiology, which leads the epidemiology study from the molecular epidemiology era to the era of genome wide association studies(GWAS). Here we review the epidemiological studies of EC(especially ESCC) in the era of GWAS, and provide an overview of the general risk factors and those genomic variants(genes, SNPs, miRNAs, proteins) involved in the process of ESCC.

  7. Utilizing genomics to study entomopathogenicity in the fungal phylum Entomophthoromycota

    DEFF Research Database (Denmark)

    de Fine Licht, Henrik Hjarvard; Hajek, Ann E.; Eilenberg, Jørgen

    2016-01-01

    primers, expressed sequence tag methodology or de novo transcriptome sequencing with molecular function inferred by homology analysis; and third, primarily forthcoming whole-genome sequencing data sets. Here we summarize the current genetic resources for Entomophthoromycota and identify research areas...

  8. 21 CFR 601.70 - Annual progress reports of postmarketing studies.

    Science.gov (United States)

    2010-04-01

    ... provide useful information. Each annual progress report shall be accompanied by a completed transmittal... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Annual progress reports of postmarketing studies... SERVICES (CONTINUED) BIOLOGICS LICENSING Postmarketing Studies § 601.70 Annual progress reports...

  9. Genome-wide association study of proneness to anger.

    Directory of Open Access Journals (Sweden)

    Eric Mick

    Full Text Available BACKGROUND: Community samples suggest that approximately 1 in 20 children and adults exhibit clinically significant anger, hostility, and aggression. Individuals with dysregulated emotional control have a greater lifetime burden of psychiatric morbidity, severe impairment in role functioning, and premature mortality due to cardiovascular disease. METHODS: With publically available data secured from dbGaP, we conducted a genome-wide association study of proneness to anger using the Spielberger State-Trait Anger Scale in the Atherosclerosis Risk in Communities (ARIC study (n = 8,747. RESULTS: Subjects were, on average, 54 (range 45-64 years old at baseline enrollment, 47% (n = 4,117 were male, and all were of European descent by self-report. The mean Angry Temperament and Angry Reaction scores were 5.8 ± 1.8 and 7.6 ± 2.2. We observed a nominally significant finding (p = 2.9E-08, λ = 1.027 - corrected pgc = 2.2E-07, λ = 1.0015 on chromosome 6q21 in the gene coding for the non-receptor protein-tyrosine kinase, Fyn. CONCLUSIONS: Fyn interacts with NDMA receptors and inositol-1,4,5-trisphosphate (IP3-gated channels to regulate calcium influx and intracellular release in the post-synaptic density. These results suggest that signaling pathways regulating intracellular calcium homeostasis, which are relevant to memory, learning, and neuronal survival, may in part underlie the expression of Angry Temperament.

  10. A genome-wide association study in multiple system atrophy

    Science.gov (United States)

    Sailer, Anna; Nalls, Michael A.; Schulte, Claudia; Federoff, Monica; Price, T. Ryan; Lees, Andrew; Ross, Owen A.; Dickson, Dennis W.; Mok, Kin; Mencacci, Niccolo E.; Schottlaender, Lucia; Chelban, Viorica; Ling, Helen; O'Sullivan, Sean S.; Wood, Nicholas W.; Traynor, Bryan J.; Ferrucci, Luigi; Federoff, Howard J.; Mhyre, Timothy R.; Morris, Huw R.; Deuschl, Günther; Quinn, Niall; Widner, Hakan; Albanese, Alberto; Infante, Jon; Bhatia, Kailash P.; Poewe, Werner; Oertel, Wolfgang; Höglinger, Günter U.; Wüllner, Ullrich; Goldwurm, Stefano; Pellecchia, Maria Teresa; Ferreira, Joaquim; Tolosa, Eduardo; Bloem, Bastiaan R.; Rascol, Olivier; Meissner, Wassilios G.; Hardy, John A.; Revesz, Tamas; Holton, Janice L.; Gasser, Thomas; Wenning, Gregor K.; Singleton, Andrew B.

    2016-01-01

    Objective: To identify genetic variants that play a role in the pathogenesis of multiple system atrophy (MSA), we undertook a genome-wide association study (GWAS). Methods: We performed a GWAS with >5 million genotyped and imputed single nucleotide polymorphisms (SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA cases were collected from North American and European centers, one third of which were neuropathologically confirmed. Results: We found no significant loci after stringent multiple testing correction. A number of regions emerged as potentially interesting for follow-up at p < 1 × 10−6, including SNPs in the genes FBXO47, ELOVL7, EDN1, and MAPT. Contrary to previous reports, we found no association of the genes SNCA and COQ2 with MSA. Conclusions: We present a GWAS in MSA. We have identified several potentially interesting gene loci, including the MAPT locus, whose significance will have to be evaluated in a larger sample set. Common genetic variation in SNCA and COQ2 does not seem to be associated with MSA. In the future, additional samples of well-characterized patients with MSA will need to be collected to perform a larger MSA GWAS, but this initial study forms the basis for these next steps. PMID:27629089

  11. Drawing the line between commensal and pathogenic Gardnerella vaginalis through genome analysis and virulence studies

    Directory of Open Access Journals (Sweden)

    Girerd Philippe H

    2010-06-01

    Full Text Available Abstract Background Worldwide, bacterial vaginosis (BV is the most common vaginal disorder. It is associated with risk for preterm birth and HIV infection. The etiology of the condition has been debated for nearly half a century and the lack of knowledge about its cause and progression has stymied efforts to improve therapy and prevention. Gardnerella vaginalis was originally identified as the causative agent, but subsequent findings that it is commonly isolated from seemingly healthy women cast doubt on this claim. Recent studies shedding light on the virulence properties of G. vaginalis, however, have drawn the species back into the spotlight. Results In this study, we sequenced the genomes of a strain of G. vaginalis from a healthy woman, and one from a woman with bacterial vaginosis. Comparative analysis of the genomes revealed significant divergence and in vitro studies indicated disparities in the virulence potential of the two strains. The commensal isolate exhibited reduced cytotoxicity and yet the cytolysin proteins encoded by the two strains were nearly identical, differing at a single amino acid, and were transcribed at similar levels. The BV-associated strain encoded a different variant of a biofilm associated protein gene and demonstrated greater adherence, aggregation, and biofilm formation. Using filters with different pore sizes, we found that direct contact between the bacteria and epithelial cells is required for cytotoxicity. Conclusions The results indicated that contact is required for cytotoxicity and suggested that reduced cytotoxicity in the commensal isolate could be due to impaired adherence. This study outlines two distinct genotypic variants of G. vaginalis, one apparently commensal and one pathogenic, and presents evidence for disparate virulence potentials.

  12. The KRAB Zinc Finger Protein Roma/Zfp157 Is a Critical Regulator of Cell-Cycle Progression and Genomic Stability

    Directory of Open Access Journals (Sweden)

    Teresa L.F. Ho

    2016-04-01

    Full Text Available Regulation of DNA replication and cell division is essential for tissue growth and maintenance of genomic integrity and is particularly important in tissues that undergo continuous regeneration such as mammary glands. We have previously shown that disruption of the KRAB-domain zinc finger protein Roma/Zfp157 results in hyperproliferation of mammary epithelial cells (MECs during pregnancy. Here, we delineate the mechanism by which Roma engenders this phenotype. Ablation of Roma in MECs leads to unscheduled proliferation, replication stress, DNA damage, and genomic instability. Furthermore, mouse embryonic fibroblasts (MEFs depleted for Roma exhibit downregulation of p21Cip1 and geminin and have accelerated replication fork velocities, which is accompanied by a high rate of mitotic errors and polyploidy. In contrast, overexpression of Roma in MECs halts cell-cycle progression, whereas siRNA-mediated p21Cip1 knockdown ameliorates, in part, this phenotype. Thus, Roma is an essential regulator of the cell cycle and is required to maintain genomic stability.

  13. Genomic understanding of dinoflagellates.

    Science.gov (United States)

    Lin, Senjie

    2011-01-01

    The phylum of dinoflagellates is characterized by many unusual and interesting genomic and physiological features, the imprint of which, in its immense genome, remains elusive. Much novel understanding has been achieved in the last decade on various aspects of dinoflagellate biology, but most remarkably about the structure, expression pattern and epigenetic modification of protein-coding genes in the nuclear and organellar genomes. Major findings include: 1) the great diversity of dinoflagellates, especially at the base of the dinoflagellate tree of life; 2) mini-circularization of the genomes of typical dinoflagellate plastids (with three membranes, chlorophylls a, c1 and c2, and carotenoid peridinin), the scrambled mitochondrial genome and the extensive mRNA editing occurring in both systems; 3) ubiquitous spliced leader trans-splicing of nuclear-encoded mRNA and demonstrated potential as a novel tool for studying dinoflagellate transcriptomes in mixed cultures and natural assemblages; 4) existence and expression of histones and other nucleosomal proteins; 5) a ribosomal protein set expected of typical eukaryotes; 6) genetic potential of non-photosynthetic solar energy utilization via proton-pump rhodopsin; 7) gene candidates in the toxin synthesis pathways; and 8) evidence of a highly redundant, high gene number and highly recombined genome. Despite this progress, much more work awaits genome-wide transcriptome and whole genome sequencing in order to unfold the molecular mechanisms underlying the numerous mysterious attributes of dinoflagellates.

  14. Domestication and plant genomes.

    Science.gov (United States)

    Tang, Haibao; Sezen, Uzay; Paterson, Andrew H

    2010-04-01

    The techniques of plant improvement have been evolving with the advancement of technology, progressing from crop domestication by Neolithic humans to scientific plant breeding, and now including DNA-based genotyping and genetic engineering. Archeological findings have shown that early human ancestors often unintentionally selected for and finally fixed a few major domestication traits over time. Recent advancement of molecular and genomic tools has enabled scientists to pinpoint changes to specific chromosomal regions and genetic loci that are responsible for dramatic morphological and other transitions that distinguish crops from their wild progenitors. Extensive studies in a multitude of additional crop species, facilitated by rapid progress in sequencing and resequencing(s) of crop genomes, will further our understanding of the genomic impact from both the unusual population history of cultivated plants and millennia of human selection.

  15. Mapping the sensory perception of apple using descriptive sensory evaluation in a genome wide association study

    OpenAIRE

    Amyotte, Beatrice; Bowen, Amy J.; Banks, Travis; Rajcan, Istvan; Somers, Daryl J.

    2017-01-01

    Breeding apples is a long-term endeavour and it is imperative that new cultivars are selected to have outstanding consumer appeal. This study has taken the approach of merging sensory science with genome wide association analyses in order to map the human perception of apple flavour and texture onto the apple genome. The goal was to identify genomic associations that could be used in breeding apples for improved fruit quality. A collection of 85 apple cultivars was examined over two years thr...

  16. Microbial genomics: from sequence to function.

    OpenAIRE

    Schwartz, I

    2000-01-01

    The era of genomics (the study of genes and their function) began a scant dozen years ago with a suggestion by James Watson that the complete DNA sequence of the human genome be determined. Since that time, the human genome project has attracted a great deal of attention in the scientific world and the general media; the scope of the sequencing effort, and the extraordinary value that it will provide, has served to mask the enormous progress in sequencing other genomes. Microbial genome seque...

  17. The Progress of Metabolomics Study in Traditional Chinese Medicine Research.

    Science.gov (United States)

    Wang, Pengcheng; Wang, Qiuhong; Yang, Bingyou; Zhao, Shan; Kuang, Haixue

    2015-01-01

    Traditional Chinese medicine (TCM) has played important roles in health protection and disease treatment for thousands of years in China and has gained the gradual acceptance of the international community. However, many intricate issues, which cannot be explained by traditional methods, still remain, thus, new ideas and technologies are needed. As an emerging system biology technology, the holistic view adopted by metabolomics is similar to that of TCM, which allows us to investigate TCM with complicated conditions and multiple factors in depth. In this paper, we tried to give a timely and comprehensive update about the methodology progression of metabolomics, as well as its applications, in different fields of TCM studies including quality control, processing, safety and efficacy evaluation. The herbs investigated by metabolomics were selected for detailed examination, including Anemarrhena asphodeloides Bunge, Atractylodes macrocephala Kidd, Pinellia ternate, etc.; furthermore, some valuable results have been obtained and summarized. In conclusion, although the study of metabolomics is at the early phase and requires further scrutiny and validation, it still provides bright prospects to dissect the synergistic action of multiple components from TCM. Overall, with the further development of analytical techniques, especially multi-analysis techniques, we expect that metabolomics will greatly promote TCM research and the establishment of international standards, which is beneficial to TCM modernization.

  18. Semantically enabling a genome-wide association study database

    Directory of Open Access Journals (Sweden)

    Beck Tim

    2012-12-01

    Full Text Available Abstract Background The amount of data generated from genome-wide association studies (GWAS has grown rapidly, but considerations for GWAS phenotype data reuse and interchange have not kept pace. This impacts on the work of GWAS Central – a free and open access resource for the advanced querying and comparison of summary-level genetic association data. The benefits of employing ontologies for standardising and structuring data are widely accepted. The complex spectrum of observed human phenotypes (and traits, and the requirement for cross-species phenotype comparisons, calls for reflection on the most appropriate solution for the organisation of human phenotype data. The Semantic Web provides standards for the possibility of further integration of GWAS data and the ability to contribute to the web of Linked Data. Results A pragmatic consideration when applying phenotype ontologies to GWAS data is the ability to retrieve all data, at the most granular level possible, from querying a single ontology graph. We found the Medical Subject Headings (MeSH terminology suitable for describing all traits (diseases and medical signs and symptoms at various levels of granularity and the Human Phenotype Ontology (HPO most suitable for describing phenotypic abnormalities (medical signs and symptoms at the most granular level. Diseases within MeSH are mapped to HPO to infer the phenotypic abnormalities associated with diseases. Building on the rich semantic phenotype annotation layer, we are able to make cross-species phenotype comparisons and publish a core subset of GWAS data as RDF nanopublications. Conclusions We present a methodology for applying phenotype annotations to a comprehensive genome-wide association dataset and for ensuring compatibility with the Semantic Web. The annotations are used to assist with cross-species genotype and phenotype comparisons. However, further processing and deconstructions of terms may be required to facilitate automatic

  19. Case-Control Genome-Wide Association Study of Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Neale, Benjamin M.; Medland, Sarah; Ripke, Stephan; Anney, Richard J. L.; Asherson, Philip; Buitelaar, Jan; Franke, Barbara; Gill, Michael; Kent, Lindsey; Holmans, Peter; Middleton, Frank; Thapar, Anita; Lesch, Klaus-Peter; Faraone, Stephen V.; Daly, Mark; Nguyen, Thuy Trang; Schafer, Helmut; Steinhausen, Hans-Christoph; Reif, Andreas; Renner, Tobias J.; Romanos, Marcel; Romanos, Jasmin; Warnke, Andreas; Walitza, Susanne; Freitag, Christine; Meyer, Jobst; Palmason, Haukur; Rothenberger, Aribert; Hawi, Ziarih; Sergeant, Joseph; Roeyers, Herbert; Mick, Eric; Biederman, Joseph

    2010-01-01

    Objective: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. Thus additional genome-wide association studies (GWAS) are needed. Method: We used case-control analyses of 896 cases…

  20. Meta-Analysis of Genome-Wide Association Studies of Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Neale, Benjamin M.; Medland, Sarah E.; Ripke, Stephan; Asherson, Philip; Franke, Barbara; Lesch, Klaus-Peter; Faraone, Stephen V.; Nguyen, Thuy Trang; Schafer, Helmut; Holmans, Peter; Daly, Mark; Steinhausen, Hans-Christoph; Freitag, Christine; Reif, Andreas; Renner, Tobias J.; Romanos, Marcel; Romanos, Jasmin; Walitza, Susanne; Warnke, Andreas; Meyer, Jobst; Palmason, Haukur; Buitelaar, Jan; Vasquez, Alejandro Arias; Lambregts-Rommelse, Nanda; Gill, Michael; Anney, Richard J. L.; Langely, Kate; O'Donovan, Michael; Williams, Nigel; Owen, Michael; Thapar, Anita; Kent, Lindsey; Sergeant, Joseph; Roeyers, Herbert; Mick, Eric; Biederman, Joseph; Doyle, Alysa; Smalley, Susan; Loo, Sandra; Hakonarson, Hakon; Elia, Josephine; Todorov, Alexandre; Miranda, Ana; Mulas, Fernando; Ebstein, Richard P.; Rothenberger, Aribert; Banaschewski, Tobias; Oades, Robert D.; Sonuga-Barke, Edmund; McGough, James; Nisenbaum, Laura; Middleton, Frank; Hu, Xiaolan; Nelson, Stan

    2010-01-01

    Objective: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. As prior genome-wide association studies (GWAS) have not yielded significant results, we conducted a meta-analysis of…

  1. Meta-analysis of genome-wide association studies of attention-deficit/hyperactivity disorder.

    NARCIS (Netherlands)

    Neale, B.M.; Medland, S.E.; Ripke, S.; Asherson, P.; Franke, B.; Lesch, K.P.; Faraone, S.V.; Nguyen, T.T.; Schafer, H.; Holmans, P.; Daly, M.; Steinhausen, H.C.; Freitag, C.; Reif, A.; Renner, T.J.; Romanos, M.; Romanos, J.; Walitza, S.; Warnke, A.; Meyer, J.; Palmason, H.; Buitelaar, J.K.; Vasquez, A.A.; Lambregts-Rommelse, N.N.J.; Gill, M.; Anney, R.J.; Langely, K.; O'Donovan, M.; Williams, N.; Owen, M.; Thapar, A.; Kent, L.; Sergeant, J.A.; Roeyers, H.; Mick, E.; Biederman, J.; Doyle, A.; Smalley, S.; Loo, S.; Hakonarson, H.; Elia, J.; Todorov, A.; Miranda, A.; Mulas, F.; Ebstein, R.P.; Rothenberger, A.; Banaschewski, T.; Oades, R.D.; Sonuga-Barke, E.; McGough, J.; Nisenbaum, L.; Middleton, F.; Hu, X.; Nelson, S.

    2010-01-01

    OBJECTIVE: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. As prior genome-wide association studies (GWAS) have not yielded signifi

  2. Meta-Analysis of Genome-Wide Association Studies of Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Neale, Benjamin M.; Medland, Sarah E.; Ripke, Stephan; Asherson, Philip; Franke, Barbara; Lesch, Klaus-Peter; Faraone, Stephen V.; Nguyen, Thuy Trang; Schafer, Helmut; Holmans, Peter; Daly, Mark; Steinhausen, Hans-Christoph; Freitag, Christine; Reif, Andreas; Renner, Tobias J.; Romanos, Marcel; Romanos, Jasmin; Walitza, Susanne; Warnke, Andreas; Meyer, Jobst; Palmason, Haukur; Buitelaar, Jan; Vasquez, Alejandro Arias; Lambregts-Rommelse, Nanda; Gill, Michael; Anney, Richard J. L.; Langely, Kate; O'Donovan, Michael; Williams, Nigel; Owen, Michael; Thapar, Anita; Kent, Lindsey; Sergeant, Joseph; Roeyers, Herbert; Mick, Eric; Biederman, Joseph; Doyle, Alysa; Smalley, Susan; Loo, Sandra; Hakonarson, Hakon; Elia, Josephine; Todorov, Alexandre; Miranda, Ana; Mulas, Fernando; Ebstein, Richard P.; Rothenberger, Aribert; Banaschewski, Tobias; Oades, Robert D.; Sonuga-Barke, Edmund; McGough, James; Nisenbaum, Laura; Middleton, Frank; Hu, Xiaolan; Nelson, Stan

    2010-01-01

    Objective: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. As prior genome-wide association studies (GWAS) have not yielded significant results, we conducted a meta-analysis of…

  3. INTEGRATED GENOME-BASED STUDIES OF SHEWANELLA ECOPHYSIOLOGY

    Energy Technology Data Exchange (ETDEWEB)

    NEALSON, KENNETH H.

    2013-10-15

    This project had as its goals the understanding of the ecophysiology of the genus Shewanella using various genomics approaches. As opposed to other programs involving Shewanella, this one branched out into the various areas in which Shewanella cells are active, and included both basic and applied studies. All of the work was, to some extent, related to the ability of the bacteria to accomplish electron exchange between the cell and solid state electron acceptors and/or electron donors, a process we call Extracellular Electron Transport, or EET. The major accomplishments related to several different areas: Basic Science Studies: 1. Genetics and genomics of nitrate reduction, resulting in elucidation of atypical nitrate reduction systems in Shewanella oneidensis (MR-1)[2]. 2. Influence of bacterial strain and growth conditions on iron reduction, showing that rates of reduction, extents of reduction, and the formation of secondary minerals were different for different strains of Shewanella [3,4,9]. 3. Comparative genomics as a tool for comparing metabolic capacities of different Shewanella strains, and for predicting growth and metabolism [6,10,15]. In these studies, collaboration with ORNL, PNNL, and 4. Basic studies of electron transport in strain MR-1, both to poised electrodes, and via conductive nanowires [12,13]. This included the first accurate measurements of electrical energy generation by a single cell during electrode growth [12], and the demonstration of electrical conductivity along the length of bacterial nanowires [13]. 5. Impact of surface charge and electron flow on cell movement, cell attachment, cell growth, and biofilm formation [7.18]. The demonstration that interaction with solid state electron acceptors resulted in increased motility [7] led to the description of a phenomenon called electrokinesis. The importance of this for biofilm formation and for electron flow was hypothesized by Nealson & Finkel [18], and is now under study in several

  4. Identification of differential translation in genome wide studies.

    Science.gov (United States)

    Larsson, Ola; Sonenberg, Nahum; Nadon, Robert

    2010-12-14

    Regulation of gene expression through translational control is a fundamental mechanism implicated in many biological processes ranging from memory formation to innate immunity and whose dysregulation contributes to human diseases. Genome wide analyses of translational control strive to identify differential translation independent of cytosolic mRNA levels. For this reason, most studies measure genes' translation levels as log ratios (translation levels divided by corresponding cytosolic mRNA levels obtained in parallel). Counterintuitively, arising from a mathematical necessity, these log ratios tend to be highly correlated with the cytosolic mRNA levels. Accordingly, they do not effectively correct for cytosolic mRNA level and generate substantial numbers of biological false positives and false negatives. We show that analysis of partial variance, which produces estimates of translational activity that are independent of cytosolic mRNA levels, is a superior alternative. When combined with a variance shrinkage method for estimating error variance, analysis of partial variance has the additional benefit of having greater statistical power and identifying fewer genes as translationally regulated resulting merely from unrealistically low variance estimates rather than from large changes in translational activity. In contrast to log ratios, this formal analytical approach estimates translation effects in a statistically rigorous manner, eliminates the need for inefficient and error-prone heuristics, and produces results that agree with biological function. The method is applicable to datasets obtained from both the commonly used polysome microarray method and the sequencing-based ribosome profiling method.

  5. Genome-wide studies of telomere biology in budding yeast

    Directory of Open Access Journals (Sweden)

    Yaniv Harari

    2014-03-01

    Full Text Available Telomeres are specialized DNA-protein structures at the ends of eukaryotic chromosomes. Telomeres are essential for chromosomal stability and integrity, as they prevent chromosome ends from being recognized as double strand breaks. In rapidly proliferating cells, telomeric DNA is synthesized by the enzyme telomerase, which copies a short template sequence within its own RNA moiety, thus helping to solve the “end-replication problem”, in which information is lost at the ends of chromosomes with each DNA replication cycle. The basic mechanisms of telomere length, structure and function maintenance are conserved among eukaryotes. Studies in the yeast Saccharomyces cerevisiae have been instrumental in deciphering the basic aspects of telomere biology. In the last decade, technical advances, such as the availability of mutant collections, have allowed carrying out systematic genome-wide screens for mutants affecting various aspects of telomere biology. In this review we summarize these efforts, and the insights that this Systems Biology approach has produced so far.

  6. A Review of Study Designs and Statistical Methods for Genomic Epidemiology Studies using Next Generation Sequencing

    Directory of Open Access Journals (Sweden)

    Qian eWang

    2015-04-01

    Full Text Available Results from numerous linkage and association studies have greatly deepened scientists’ understanding of the genetic basis of many human diseases, yet some important questions remain unanswered. For example, although a large number of disease-associated loci have been identified from genome-wide association studies (GWAS in the past 10 years, it is challenging to interpret these results as most disease-associated markers have no clear functional roles in disease etiology, and all the identified genomic factors only explain a small portion of disease heritability. With the help of next-generation sequencing (NGS, diverse types of genomic and epigenetic variations can be detected with high accuracy. More importantly, instead of using linkage disequilibrium to detect association signals based on a set of pre-set probes, NGS allows researchers to directly study all the variants in each individual, therefore promises opportunities for identifying functional variants and a more comprehensive dissection of disease heritability. Although the current scale of NGS studies is still limited due to the high cost, the success of several recent studies suggests the great potential for applying NGS in genomic epidemiology, especially as the cost of sequencing continues to drop. In this review, we discuss several pioneer applications of NGS, summarize scientific discoveries for rare and complex diseases, and compare various study designs including targeted sequencing and whole-genome sequencing using population-based and family-based cohorts. Finally, we highlight recent advancements in statistical methods proposed for sequencing analysis, including group-based association tests, meta-analysis techniques, and annotation tools for variant prioritization.

  7. 1990 Flathead Valley duck nesting study progress report

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This informal progress report describes predator removal practices in the Lake County area, and observed waterfowl nest success. Species-specific data are...

  8. Progress report no. 1 : Prairie grouse population and habitat studies

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Progress report on the wildlife management of prairie grouse. A census of sharp-tailed grouse dancing grounds was again made to determine the population for the...

  9. Progress in studies of natural gas conversion in China

    Institute of Scientific and Technical Information of China (English)

    Yu Changchun; Shen Shikong

    2008-01-01

    Progress in natural gas conversion in China is presented in this paper, including processes of natural gas to synthesis gas (syngas), syngas to liquid hydrocarbons, oxygenates synthesis, methanol to olefins (MTO), methane to aromatics and oxidative coupling of methane (OCM).

  10. 新型基因组编辑技术研究进展%Progress on Novel Genome Editing Technologies

    Institute of Scientific and Technical Information of China (English)

    韩勇; 杨杰; 李子彬; 董宋鹏; 高凤山

    2015-01-01

    Genome editing is a new technology which can modifiy the targeted biological genome accurately so as to knock out some genes site-directly and integrate some exogenous genes site-directly.Recently,sev-eral effective tools were developed quickly,including engineered nuclease mediated zinc-finger nucleases (ZFN),transcription activator-like effector nucleases (TALEN)and clustered regularly interspaced short palindromic repeats along with cas9 protein (CRISPRs/Cas9),and they all can site-directly edit genomes by recognizing the target sites according to the specific structure followed by nuclease cleavage.The three no-vel genome editing technologies have been applied broadly in life science because of their advantages of higher efficiency,making easily and timesaving.Here the characteristics,principles,construction methods of the three novel genome editing technologies and their application in conventional biology model,functional genome screening,and gene therapy for human inherited diseases were reviewed.%基因组编辑技术是一种能精确靶向修饰生物基因组,实现对基因定点敲除和外源基因定点整合的技术。新出现的锌指核酸酶(ZFN)、转录激活子样效应因子核酸酶(TALEN)和规律性重复短回文序列簇与 Cas9蛋白(CRISPRs/Cas9)系统3种新型的基因组编辑技术通过特异性结构识别靶位点,核酸酶发挥切割作用对靶位点进行定点编辑。3种新型基因编辑技术因具有高效准确、制作简单、耗时短等特点而在生命科学研究中得到广泛应用。论文对目前三种新型的基因组定点编辑技术的特点、结构原理、构建方法以及在传统生物模型、功能基因筛选、人类遗传病基因治疗等方面中的应用做一综述。

  11. Study of progressive depigmentation of dog′s muzzle

    Directory of Open Access Journals (Sweden)

    Shah K

    1991-01-01

    Full Text Available A new animal model is developed using dog′s muzzle to demonstrate progressive depigmen-tation after birth. Dog′s muzzle is heavily pigmented with pigment melanin and looks black in colour. Progressive depigmentation was observed two months after birth in a pup born with a depigmented mucous membrane of the mouth and lips. This resembles the vitiligo of humans.

  12. (Post-)genomics approaches in fungal research

    NARCIS (Netherlands)

    Aguilar-Pontes, María Victoria; de Vries, Ronald P; Zhou, M.; van den Brink, J.

    2014-01-01

    To date, hundreds of fungal genomes have been sequenced and many more are in progress. This wealth of genomic information has provided new directions to study fungal biodiversity. However, to further dissect and understand the complicated biological mechanisms involved in fungal life styles, functio

  13. Susceptibility to Chronic Mucus Hypersecretion, a Genome Wide Association Study

    Science.gov (United States)

    Dijkstra, Akkelies E.; Smolonska, Joanna; van den Berge, Maarten; Wijmenga, Ciska; Zanen, Pieter; Luinge, Marjan A.; Platteel, Mathieu; Lammers, Jan-Willem; Dahlback, Magnus; Tosh, Kerrie; Hiemstra, Pieter S.; Sterk, Peter J.; Spira, Avi; Vestbo, Jorgen; Nordestgaard, Borge G.; Benn, Marianne; Nielsen, Sune F.; Dahl, Morten; Verschuren, W. Monique; Picavet, H. Susan J.; Smit, Henriette A.; Owsijewitsch, Michael; Kauczor, Hans U.; de Koning, Harry J.; Nizankowska-Mogilnicka, Eva; Mejza, Filip; Nastalek, Pawel; van Diemen, Cleo C.; Cho, Michael H.; Silverman, Edwin K.; Crapo, James D.; Beaty, Terri H.; Lomas, David A.; Bakke, Per; Gulsvik, Amund; Bossé, Yohan; Obeidat, M. A.; Loth, Daan W.; Lahousse, Lies; Rivadeneira, Fernando; Uitterlinden, Andre G.; Hofman, Andre; Stricker, Bruno H.; Brusselle, Guy G.; van Duijn, Cornelia M.; Brouwer, Uilke; Koppelman, Gerard H.; Vonk, Judith M.; Nawijn, Martijn C.; Groen, Harry J. M.; Timens, Wim; Boezen, H. Marike; Postma, Dirkje S.

    2014-01-01

    Background Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations. Methods GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP). Results A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25×10−6, OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3×10−9) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture. Conclusions Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH. PMID:24714607

  14. Susceptibility to chronic mucus hypersecretion, a genome wide association study.

    Directory of Open Access Journals (Sweden)

    Akkelies E Dijkstra

    Full Text Available BACKGROUND: Chronic mucus hypersecretion (CMH is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA study of CMH in Caucasian populations. METHODS: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years. Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP. RESULTS: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25×10(-6, OR = 1.17, located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1 on chromosome 3. The risk allele (G was associated with higher mRNA expression of SATB1 (4.3×10(-9 in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture. CONCLUSIONS: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH.

  15. [Chronologic study of signs of myocardiopathy in progressive muscular dystrophy].

    Science.gov (United States)

    Barona Zamora, P; Narbona García, J; Alvarez Gómez, M J; Fidalgo Andrés, M L; Sáenz de Buruaga, J; Villa Elizaga, I

    1993-02-01

    In order to analyze the evolution of cardiomyopathy in progressive muscular dystrophies, thirty-three patients (17 with Duchenne type, 11 with Becker type and 5 with the autosomal recessive type dystrophy) were studied retrospectively. Cardiac and systemic follow-up every 3-6 months was made in 29 patients. The electrocardiogram was the first test that became altered, followed by the echocardiogram and thoracic radiograph and finally heart failure manifestations. There was a direct correlation between age and the appearance of abnormal cardiac tests. Electrocardiographic alterations, in patients who were less than 12.5 years of age, were significantly more frequent in the group with Duchenne dystrophy that in the no-Duchenne group. In regards to the appearance of the echocardiographic and radiographic abnormalities, there were no significant differences between the two groups. However, we have noticed a trend towards a more frequent and earlier presentation of these abnormalities in the Duchenne's muscular dystrophy than in the no-Duchenne group.

  16. Progress in preliminary studies at Ottana Solar Facility

    Science.gov (United States)

    Demontis, V.; Camerada, M.; Cau, G.; Cocco, D.; Damiano, A.; Melis, T.; Musio, M.

    2016-05-01

    The fast increasing share of distributed generation from non-programmable renewable energy sources, such as the strong penetration of photovoltaic technology in the distribution networks, has generated several problems for the management and security of the whole power grid. In order to meet the challenge of a significant share of solar energy in the electricity mix, several actions aimed at increasing the grid flexibility and its hosting capacity, as well as at improving the generation programmability, need to be investigated. This paper focuses on the ongoing preliminary studies at the Ottana Solar Facility, a new experimental power plant located in Sardinia (Italy) currently under construction, which will offer the possibility to progress in the study of solar plants integration in the power grid. The facility integrates a concentrating solar power (CSP) plant, including a thermal energy storage system and an organic Rankine cycle (ORC) unit, with a concentrating photovoltaic (CPV) plant and an electrical energy storage system. The facility has the main goal to assess in real operating conditions the small scale concentrating solar power technology and to study the integration of the two technologies and the storage systems to produce programmable and controllable power profiles. A model for the CSP plant yield was developed to assess different operational strategies that significantly influence the plant yearly yield and its global economic effectiveness. In particular, precise assumptions for the ORC module start-up operation behavior, based on discussions with the manufacturers and technical datasheets, will be described. Finally, the results of the analysis of the: "solar driven", "weather forecasts" and "combined storage state of charge (SOC)/ weather forecasts" operational strategies will be presented.

  17. Genome-wide association study with 1000 genomes imputation identifies signals for nine sex hormone-related phenotypes.

    Science.gov (United States)

    Ruth, Katherine S; Campbell, Purdey J; Chew, Shelby; Lim, Ee Mun; Hadlow, Narelle; Stuckey, Bronwyn G A; Brown, Suzanne J; Feenstra, Bjarke; Joseph, John; Surdulescu, Gabriela L; Zheng, Hou Feng; Richards, J Brent; Murray, Anna; Spector, Tim D; Wilson, Scott G; Perry, John R B

    2016-02-01

    Genetic factors contribute strongly to sex hormone levels, yet knowledge of the regulatory mechanisms remains incomplete. Genome-wide association studies (GWAS) have identified only a small number of loci associated with sex hormone levels, with several reproductive hormones yet to be assessed. The aim of the study was to identify novel genetic variants contributing to the regulation of sex hormones. We performed GWAS using genotypes imputed from the 1000 Genomes reference panel. The study used genotype and phenotype data from a UK twin register. We included 2913 individuals (up to 294 males) from the Twins UK study, excluding individuals receiving hormone treatment. Phenotypes were standardised for age, sex, BMI, stage of menstrual cycle and menopausal status. We tested 7,879,351 autosomal SNPs for association with levels of dehydroepiandrosterone sulphate (DHEAS), oestradiol, free androgen index (FAI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, progesterone, sex hormone-binding globulin and testosterone. Eight independent genetic variants reached genome-wide significance (Phormone regulation.

  18. The Chlamydomonas genome project: a decade on

    Science.gov (United States)

    Blaby, Ian K.; Blaby-Haas, Crysten; Tourasse, Nicolas; Hom, Erik F. Y.; Lopez, David; Aksoy, Munevver; Grossman, Arthur; Umen, James; Dutcher, Susan; Porter, Mary; King, Stephen; Witman, George; Stanke, Mario; Harris, Elizabeth H.; Goodstein, David; Grimwood, Jane; Schmutz, Jeremy; Vallon, Olivier; Merchant, Sabeeha S.; Prochnik, Simon

    2014-01-01

    The green alga Chlamydomonas reinhardtii is a popular unicellular organism for studying photosynthesis, cilia biogenesis and micronutrient homeostasis. Ten years since its genome project was initiated, an iterative process of improvements to the genome and gene predictions has propelled this organism to the forefront of the “omics” era. Housed at Phytozome, the Joint Genome Institute’s (JGI) plant genomics portal, the most up-to-date genomic data include a genome arranged on chromosomes and high-quality gene models with alternative splice forms supported by an abundance of RNA-Seq data. Here, we present the past, present and future of Chlamydomonas genomics. Specifically, we detail progress on genome assembly and gene model refinement, discuss resources for gene annotations, functional predictions and locus ID mapping between versions and, importantly, outline a standardized framework for naming genes. PMID:24950814

  19. The genomics of adaptation.

    Science.gov (United States)

    Radwan, Jacek; Babik, Wiesław

    2012-12-22

    The amount and nature of genetic variation available to natural selection affect the rate, course and outcome of evolution. Consequently, the study of the genetic basis of adaptive evolutionary change has occupied biologists for decades, but progress has been hampered by the lack of resolution and the absence of a genome-level perspective. Technological advances in recent years should now allow us to answer many long-standing questions about the nature of adaptation. The data gathered so far are beginning to challenge some widespread views of the way in which natural selection operates at the genomic level. Papers in this Special Feature of Proceedings of the Royal Society B illustrate various aspects of the broad field of adaptation genomics. This introductory article sets up a context and, on the basis of a few selected examples, discusses how genomic data can advance our understanding of the process of adaptation.

  20. Genome Studies on Nematophagous and Entomogenous Fungi in China

    Directory of Open Access Journals (Sweden)

    Weiwei Zhang

    2016-02-01

    Full Text Available The nematophagous and entomogenous fungi are natural enemies of nematodes and insects and have been utilized by humans to control agricultural and forestry pests. Some of these fungi have been or are being developed as biological control agents in China and worldwide. Several important nematophagous and entomogenous fungi, including nematode-trapping fungi (Arthrobotrys oligospora and Drechslerella stenobrocha, nematode endoparasite (Hirsutella minnesotensis, insect pathogens (Beauveria bassiana and Metarhizium spp. and Chinese medicinal fungi (Ophiocordyceps sinensis and Cordyceps militaris, have been genome sequenced and extensively analyzed in China. The biology, evolution, and pharmaceutical application of these fungi and their interacting with host nematodes and insects revealed by genomes, comparing genomes coupled with transcriptomes are summarized and reviewed in this paper.

  1. Databases and web tools for cancer genomics study.

    Science.gov (United States)

    Yang, Yadong; Dong, Xunong; Xie, Bingbing; Ding, Nan; Chen, Juan; Li, Yongjun; Zhang, Qian; Qu, Hongzhu; Fang, Xiangdong

    2015-02-01

    Publicly-accessible resources have promoted the advance of scientific discovery. The era of genomics and big data has brought the need for collaboration and data sharing in order to make effective use of this new knowledge. Here, we describe the web resources for cancer genomics research and rate them on the basis of the diversity of cancer types, sample size, omics data comprehensiveness, and user experience. The resources reviewed include data repository and analysis tools; and we hope such introduction will promote the awareness and facilitate the usage of these resources in the cancer research community.

  2. Databases and Web Tools for Cancer Genomics Study

    Institute of Scientific and Technical Information of China (English)

    Yadong Yang; Xunong Dong; Bingbing Xie; Nan Ding; Juan Chen; Yongjun Li; Qian Zhang; Hongzhu Qu; Xiangdong Fang

    2015-01-01

    Publicly-accessible resources have promoted the advance of scientific discovery. The era of genomics and big data has brought the need for collaboration and data sharing in order to make effective use of this new knowledge. Here, we describe the web resources for cancer genomics research and rate them on the basis of the diversity of cancer types, sample size, omics data com-prehensiveness, and user experience. The resources reviewed include data repository and analysis tools;and we hope such introduction will promote the awareness and facilitate the usage of these resources in the cancer research community.

  3. Layers of epistasis: genome-wide regulatory networks and network approaches to genome-wide association studies

    Science.gov (United States)

    Cowper-Sal·lari, Richard; Cole, Michael D.; Karagas, Margaret R.; Lupien, Mathieu; Moore, Jason H.

    2010-01-01

    The conceptual foundation of the genome-wide association study (GWAS) has advanced unchecked since its conception. A revision might seem premature as the potential of GWAS has not been fully realized. Multiple technical and practical limitations need to be overcome before GWAS can be fairly criticized. But with the completion of hundreds of studies and a deeper understanding of the genetic architecture of disease, warnings are being raised. The results compiled to date indicate that risk-associated variants lie predominantly in non-coding regions of the genome. Additionally, alternative methodologies are uncovering large and heterogeneous sets of rare variants underlying disease. The fear is that, even in its fulfilment, the current GWAS paradigm might be incapable of dissecting all kinds of phenotypes. In the following text we review several initiatives that aim to overcome these limitations. The overarching theme of these studies is the inclusion of biological knowledge to both the analysis and interpretation of genotyping data. GWAS is uninformed of biology by design and although there is some virtue in its simplicity it is also its most conspicuous deficiency. We propose a framework in which to integrate these novel approaches, both empirical and theoretical, in the form of a genome-wide regulatory network (GWRN). By processing experimental data into networks, emerging data types based on chromatin-immunoprecipitation are made computationally tractable. This will give GWAS re-analysis efforts the most current and relevant substrates, and root them firmly on our knowledge of human disease. PMID:21197657

  4. The Yak genome database: an integrative database for studying yak biology and high-altitude adaption.

    Science.gov (United States)

    Hu, Quanjun; Ma, Tao; Wang, Kun; Xu, Ting; Liu, Jianquan; Qiu, Qiang

    2012-11-07

    The yak (Bos grunniens) is a long-haired bovine that lives at high altitudes and is an important source of milk, meat, fiber and fuel. The recent sequencing, assembly and annotation of its genome are expected to further our understanding of the means by which it has adapted to life at high altitudes and its ecologically important traits. The Yak Genome Database (YGD) is an internet-based resource that provides access to genomic sequence data and predicted functional information concerning the genes and proteins of Bos grunniens. The curated data stored in the YGD includes genome sequences, predicted genes and associated annotations, non-coding RNA sequences, transposable elements, single nucleotide variants, and three-way whole-genome alignments between human, cattle and yak. YGD offers useful searching and data mining tools, including the ability to search for genes by name or using function keywords as well as GBrowse genome browsers and/or BLAST servers, which can be used to visualize genome regions and identify similar sequences. Sequence data from the YGD can also be downloaded to perform local searches. A new yak genome database (YGD) has been developed to facilitate studies on high-altitude adaption and bovine genomics. The database will be continuously updated to incorporate new information such as transcriptome data and population resequencing data. The YGD can be accessed at http://me.lzu.edu.cn/yak.

  5. Application of genome editing technologies to the study and treatment of hematological disease.

    Science.gov (United States)

    Pellagatti, Andrea; Dolatshad, Hamid; Yip, Bon Ham; Valletta, Simona; Boultwood, Jacqueline

    2016-01-01

    Genome editing technologies have advanced significantly over the past few years, providing a fast and effective tool to precisely manipulate the genome at specific locations. The three commonly used genome editing technologies are Zinc Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs), and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated Cas9 (CRISPR/Cas9) system. ZFNs and TALENs consist of endonucleases fused to a DNA-binding domain, while the CRISPR/Cas9 system uses guide RNAs to target the bacterial Cas9 endonuclease to the desired genomic location. The double-strand breaks made by these endonucleases are repaired in the cells either by non-homologous end joining, resulting in the introduction of insertions/deletions, or, if a repair template is provided, by homology directed repair. The ZFNs, TALENs and CRISPR/Cas9 systems take advantage of these repair mechanisms for targeted genome modification and have been successfully used to manipulate the genome in human cells. These genome editing tools can be used to investigate gene function, to discover new therapeutic targets, and to develop disease models. Moreover, these genome editing technologies have great potential in gene therapy. Here, we review the latest advances in the application of genome editing technology to the study and treatment of hematological disorders.

  6. The Yak genome database: an integrative database for studying yak biology and high-altitude adaption

    Directory of Open Access Journals (Sweden)

    Hu Quanjun

    2012-11-01

    Full Text Available Abstract Background The yak (Bos grunniens is a long-haired bovine that lives at high altitudes and is an important source of milk, meat, fiber and fuel. The recent sequencing, assembly and annotation of its genome are expected to further our understanding of the means by which it has adapted to life at high altitudes and its ecologically important traits. Description The Yak Genome Database (YGD is an internet-based resource that provides access to genomic sequence data and predicted functional information concerning the genes and proteins of Bos grunniens. The curated data stored in the YGD includes genome sequences, predicted genes and associated annotations, non-coding RNA sequences, transposable elements, single nucleotide variants, and three-way whole-genome alignments between human, cattle and yak. YGD offers useful searching and data mining tools, including the ability to search for genes by name or using function keywords as well as GBrowse genome browsers and/or BLAST servers, which can be used to visualize genome regions and identify similar sequences. Sequence data from the YGD can also be downloaded to perform local searches. Conclusions A new yak genome database (YGD has been developed to facilitate studies on high-altitude adaption and bovine genomics. The database will be continuously updated to incorporate new information such as transcriptome data and population resequencing data. The YGD can be accessed at http://me.lzu.edu.cn/yak.

  7. Genome-wide association study of insect bite hypersensitivity in Dutch Shetland pony mares

    NARCIS (Netherlands)

    Schurink, A.; Ducro, B.J.; Bastiaansen, J.W.M.; Frankena, K.; Arendonk, van J.A.M.

    2013-01-01

    Insect bite hypersensitivity (IBH) is the most common allergic disease present in horses worldwide. It has been shown that IBH is under genetic control, but the knowledge of associated genes is limited. We conducted a genome-wide association study to identify and quantify genomic regions contributin

  8. Implementing Meta-analysis for genome-wide association studies of pork quality traits

    Science.gov (United States)

    Pork quality is a critical concern in the meat industry. Implementation of genome-wide association studies (GWA) allows identification of genomic regions that explain a substantial portion of the variation of relevant traits. It is also important to determine the consistency of results of GWA across...

  9. Genome-Wide Association Study and Linkage Analysis of the Healthy Aging Index

    DEFF Research Database (Denmark)

    Minster, Ryan L; Sanders, Jason L; Singh, Jatinder;

    2015-01-01

    BACKGROUND: The Healthy Aging Index (HAI) is a tool for measuring the extent of health and disease across multiple systems. METHODS: We conducted a genome-wide association study and a genome-wide linkage analysis to map quantitative trait loci associated with the HAI and a modified HAI weighted...

  10. More heritability probably captured by psoriasis genome-wide association study in Han Chinese.

    Science.gov (United States)

    Jiang, Long; Liu, Lu; Cheng, Yuyan; Lin, Yan; Shen, Changbing; Zhu, Caihong; Yang, Sen; Yin, Xianyong; Zhang, Xuejun

    2015-11-15

    Missing heritability is a common problem in genome-wide association studies in complex diseases/traits. To quantify the unbiased heritability estimate, we applied the phenotype correlation-genotype correlation regression in psoriasis genome-wide association data in Han Chinese which comprises 1139 cases and 1132 controls. We estimated that 45.7% heritability of psoriasis in Han Chinese were captured by common variants (s.e.=12.5%), which reinforced that the majority of psoriasis heritability can be covered by common variants in genome-wide association data (68.2%). The results provided evidence that the heritability covered by psoriasis genome-wide genotyping data was probably underestimated in previous restricted maximum likelihood method. Our study highlights the broad role of common variants in the etiology of psoriasis and sheds light on the possibility to identify more common variants of small effect by increasing the sample size in psoriasis genome-wide association studies.

  11. Genome-Wide Association Study of Schizophrenia in Japanese Population

    Science.gov (United States)

    Yamada, Kazuo; Iwayama, Yoshimi; Hattori, Eiji; Iwamoto, Kazuya; Toyota, Tomoko; Ohnishi, Tetsuo; Ohba, Hisako; Maekawa, Motoko; Kato, Tadafumi; Yoshikawa, Takeo

    2011-01-01

    Schizophrenia is a devastating neuropsychiatric disorder with genetically complex traits. Genetic variants should explain a considerable portion of the risk for schizophrenia, and genome-wide association study (GWAS) is a potentially powerful tool for identifying the risk variants that underlie the disease. Here, we report the results of a three-stage analysis of three independent cohorts consisting of a total of 2,535 samples from Japanese and Chinese populations for searching schizophrenia susceptibility genes using a GWAS approach. Firstly, we examined 115,770 single nucleotide polymorphisms (SNPs) in 120 patient-parents trio samples from Japanese schizophrenia pedigrees. In stage II, we evaluated 1,632 SNPs (1,159 SNPs of p<0.01 and 473 SNPs of p<0.05 that located in previously reported linkage regions). The second sample consisted of 1,012 case-control samples of Japanese origin. The most significant p value was obtained for the SNP in the ELAVL2 [(embryonic lethal, abnormal vision, Drosophila)-like 2] gene located on 9p21.3 (p = 0.00087). In stage III, we scrutinized the ELAVL2 gene by genotyping gene-centric tagSNPs in the third sample set of 293 family samples (1,163 individuals) of Chinese descent and the SNP in the gene showed a nominal association with schizophrenia in Chinese population (p = 0.026). The current data in Asian population would be helpful for deciphering ethnic diversity of schizophrenia etiology. PMID:21674006

  12. Genome-wide association study of schizophrenia in Japanese population.

    Directory of Open Access Journals (Sweden)

    Kazuo Yamada

    Full Text Available Schizophrenia is a devastating neuropsychiatric disorder with genetically complex traits. Genetic variants should explain a considerable portion of the risk for schizophrenia, and genome-wide association study (GWAS is a potentially powerful tool for identifying the risk variants that underlie the disease. Here, we report the results of a three-stage analysis of three independent cohorts consisting of a total of 2,535 samples from Japanese and Chinese populations for searching schizophrenia susceptibility genes using a GWAS approach. Firstly, we examined 115,770 single nucleotide polymorphisms (SNPs in 120 patient-parents trio samples from Japanese schizophrenia pedigrees. In stage II, we evaluated 1,632 SNPs (1,159 SNPs of p<0.01 and 473 SNPs of p<0.05 that located in previously reported linkage regions. The second sample consisted of 1,012 case-control samples of Japanese origin. The most significant p value was obtained for the SNP in the ELAVL2 [(embryonic lethal, abnormal vision, Drosophila-like 2] gene located on 9p21.3 (p = 0.00087. In stage III, we scrutinized the ELAVL2 gene by genotyping gene-centric tagSNPs in the third sample set of 293 family samples (1,163 individuals of Chinese descent and the SNP in the gene showed a nominal association with schizophrenia in Chinese population (p = 0.026. The current data in Asian population would be helpful for deciphering ethnic diversity of schizophrenia etiology.

  13. Advancement in genetic variants conferring obesity susceptibility from genome-wide association studies.

    Science.gov (United States)

    Wang, Tao; Jia, Weiping; Hu, Cheng

    2015-06-01

    Obesity prevalence has increased in recent years. Lifestyle change fuels obesity, but genetic factors cause more than 50% of average variations in obesity. The advent of genome-wide association studies (GWAS) has hastened the progress of polygenic obesity research. As of this writing, more than 73 obesity susceptibility loci have been identified in ethnic groups through GWAS. The identified loci explain only 2% to 4% of obesity heritability, thereby indicating that a large proportion of loci remain undiscovered. Thus, the next step is to identify and confirm novel loci, which may exhibit smaller effects and lower allele frequencies than established loci. However, achieving these tasks has been difficult for researchers. GWAS help researchers discover the causal loci. Moreover, numerous biological studies have been performed on the polygenic effects on obesity, such as studies on fat mass- and obesity-associated gene (FTO), but the role of these polygenic effects in the mechanism of obesity remains unclear. Thus, obesity-causing variations should be identified, and insights into the biology of polygenic effects on obesity are needed.

  14. Developmental origins of the adipocyte lineage: new insights from genetics and genomics studies.

    Science.gov (United States)

    Billon, Nathalie; Dani, Christian

    2012-03-01

    The current epidemic of obesity and overweight has caused a surge of interest in the study of adipose tissue formation. Much progress has been made in defining the transcriptional networks controlling the terminal differentiation of adipocyte progenitors into mature adipocytes. However, the early steps of adipocyte development and the embryonic origin of this lineage have been largely disregarded until recently. In mammals, two functionally different types of adipose tissues coexist, which are both involved in energy balance but assume opposite functions. White adipose tissue (WAT) stores energy, while brown adipose tissue (BAT) is specialized in energy expenditure. WAT and BAT can be found as several depots located in various sites of the body. Individual fat depots exhibit different timing of appearance during development, as well as distinct functional properties, suggesting possible differences in their developmental origin. This hypothesis has recently been revisited through large-scale genomics studies and in vivo lineage tracing approaches, which are reviewed in this report. These studies have provided novel fundamental insights into adipocyte biology, pointing out distinct developmental origins for WAT and BAT, as well as for individual WAT depots. They suggest that the adipose tissue is composed of distinct mini-organs, exhibiting developmental and functional differences, as well as variable contribution to obesity-related metabolic diseases.

  15. Computational Study of the Genomic and Epigenomic Phenomena

    Science.gov (United States)

    Yang, Wenjing

    Biological systems are perhaps the ultimate complex systems, uniquely capable of processing and communicating information, reproducing in their lifetimes, and adapting in evolutionary time scales. My dissertation research focuses on using computational approaches to understand the biocomplexity manifested in the multitude of length scales and time scales. At the molecular and cellular level, central to the complex behavior of a biological system is the regulatory network. My research study focused on epigenetics, which is essential for multicellular organisms to establish cellular identity during development or in response to intracellular and environmental stimuli. My computational study of epigenomics is greatly facilitated by recent advances in high-throughput sequencing technology, which enables high-resolution snapshots of epigenomes and transcriptomes. Using human CD4+ T cell as a model system, the dynamical changes in epigenome and transcriptome pertinent to T cell activation were investigated at the genome scale. Going beyond traditional focus on transcriptional regulation, I provided evidences that post-transcriptional regulation may serve as a major component of the regulatory network. In addition, I explored alternative polyadenylation, another novel aspect of gene regulation, and how it cross-talks with the local chromatin structure. As the renowned theoretical biologist Theodosius Dobzhansky said eloquently, "Nothing in biology makes sense except in the light of evolution''. To better understand this ubiquitous driving force in the biological world, I went beyond molecular events in a single organism, and investigated the dynamical changes of population structure along the evolutionary time scale. To this end, we used HIV virus population dynamics in the host immune system as a model system. The evolution of HIV viral population plays a key role in AIDS immunopathogenesis with its exceptionally high mutation rate. However, the theoretical studies of

  16. Genome-wide allelotype study of primary glioblastoma multiforme

    Institute of Scientific and Technical Information of China (English)

    胡杰; 江澄川; 吴浩强; 彭颂先; 唐婉君; 陈商群

    2003-01-01

    Objective To investigate the molecular genetic pathogenesis of primary glioblastoma multiforme (GBM) and identify which chromosomes or chromosomal regions of the entire genome may harbor tumor suppressor genes (TSGs) associated with GBM.Methods A high-resolution allelotype study of 21 cases of primary GBM was performed by PCR-based loss of heterozygosity (LOH)analysis. Three hundred and eighty-two fluorescent dye-labeled microsatellite markers covering all 22 autosomes were applied. The mean genetic distance between two flanking markers was about 10 cM.Results LOH was observed on all 39 nonacrocentric autosomal arms examined in this study. The LOH frequencies of 10q, 10p, 9p, 17p and 13q were the highest (>50%). Furthermore, high LOH frequencies were detected in the regions containing known TSGs including PTEN, DMBT1, p16, p15, p53 and RB; the LOH frequencies on 14q, 3q, 22q, 11p, 9q, 19q were also high (>40.5%). Our study observed the following commonly deleted regions: 9p22-23, 10p12.2-14, 10q21.3, 13q12.1-14.1, 13q14.3-31, 17p11.2-12, 17p13, 3q25.2-26.2, 11p12-13, 14q13-31, 14q32.1, 14q11.1-13, 22q13.3, 4q35, 4q31.1-31.2, 6q27 and 6q21-23.3. Conclusions The molecular pathogenesis of GBM is very complicated and associated with a variety of genetic abnormalities on many chromosomal arms. The most closely related chromosomal arms to the pathogenesis of GBM are 10q, 10p, 9p, 17p and 13q. Besides the well-known TSGs including PTEN, DMBT1, p16, p15, p53 and RB, multiple unknown TSGs associated with GBM may be present on the commonly deleted regions detected in the present study.

  17. Evaluating Theobroma grandiflorum for comparative genomic studies with Theobroma cacao

    Science.gov (United States)

    The seeds of Theobroma cacao (cacao) are the source of cocoa, the raw material for the multi-billion dollar chocolate industry. Cacao’s two most important traits are its unique seed storage triglyceride (cocoa butter) and the flavor of its fermented beans (chocolate). The genome of T. cacao is bei...

  18. Genome-wide association study of Tourette's syndrome

    NARCIS (Netherlands)

    Scharf, J. M.; Yu, D.; Mathews, C. A.; Neale, B. M.; Stewart, S. E.; Fagerness, J. A.; Evans, P.; Gamazon, E.; Edlund, C. K.; Service, S. K.; Tikhomirov, A.; Osiecki, L.; Illmann, C.; Pluzhnikov, A.; Konkashbaev, A.; Davis, L. K.; Han, B.; Crane, J.; Moorjani, P.; Crenshaw, A. T.; Parkin, M. A.; Reus, V. I.; Lowe, T. L.; Rangel-Lugo, M.; Chouinard, S.; Dion, Y.; Girard, S.; Cath, D. C.; Smit, J. H.; King, R. A.; Fernandez, T. V.; Leckman, J. F.; Kidd, K. K.; Kidd, J. R.; Pakstis, A. J.; State, M. W.; Herrera, L. D.; Romero, R.; Fournier, E.; Sandor, P.; Barr, C. L.; Phan, N.; Gross-Tsur, V.; Benarroch, F.; Pollak, Y.; Budman, C. L.; Bruun, R. D.; Erenberg, G.; Naarden, A. L.; Lee, P. C.; Weiss, N.; Kremeyer, B.; Berrio, G. B.; Campbell, D. D.; Cardona Silgado, J. C.; Ochoa, W. C.; Mesa Restrepo, S. C.; Muller, H.; Valencia Duarte, A. V.; Lyon, G. J.; Leppert, M.; Morgan, J.; Weiss, R.; Grados, M. A.; Anderson, K.; Davarya, S.; Singer, H.; Walkup, J.; Jankovic, J.; Tischfield, J. A.; Heiman, G. A.; Gilbert, D. L.; Hoekstra, P. J.; Robertson, M. M.; Kurlan, R.; Liu, C.; Gibbs, J. R.; Singleton, A.; Hardy, J.; Strengman, E.; Ophoff, R. A.; Wagner, M.; Moessner, R.; Mirel, D. B.; Posthuma, D.; Sabatti, C.; Eskin, E.; Conti, D. V.; Knowles, J. A.; Ruiz-Linares, A.; Rouleau, G. A.; Purcell, S.; Heutink, P.; Oostra, B. A.; McMahon, W. M.; Freimer, N. B.; Cox, N. J.; Pauls, D. L.

    2013-01-01

    Tourette's syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association

  19. Progress in Predictability Studies in China(2003-2006)

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Since the last International Union of Geodesy and Geophysics General Assembly(2003),predictability studies in China have made significant progress.For dynamic forecasts,two novel approaches of conditional nonlinear optimal perturbation and nonlinear local Lyapunov exponents were proposed to cope with the predictability problems of weather and climate,which are superior to the corresponding linear theory.A (ENSO)Was provided based on a theoretical model.To improve the forecast skill of an intermediate coupled ENSO model,a new initialization scheme was developed,and its applicability was illustrated by hindcast experiments.Using the reconstruction phase space theory and the spatio-temporal series predictive method,Chinese scientists also proposed a new approach to improve dynamical extended range(monthly) prediction and successfully applied it to the monthly-scale predictability of short-term climate variations.In statistical forecasts,it Was found that the effects of sea surface temperature on precipitation in China have obvious spatial and temporal distribution features,and that summer precipitation patterns over east China are closely related to the northern atmospheric circulation.For ensemble forecasts,a new initial perturbation method was used to forecast heavy rain in Guangdong and Fujian Provinces on 8 June 1998.Additionally,the ensemble forecast approach was also used for the prediction of a tropical typhoons.A new dowuscaling model consisting of dynamical and statistical methods was provided to improve the prediction of the monthly mean precipitation.This new downscaling model showed a relatively higher score than the issued operational forecast.

  20. Modelling human regulatory variation in mouse: finding the function in genome-wide association studies and whole-genome sequencing.

    Directory of Open Access Journals (Sweden)

    Jean-François Schmouth

    Full Text Available An increasing body of literature from genome-wide association studies and human whole-genome sequencing highlights the identification of large numbers of candidate regulatory variants of potential therapeutic interest in numerous diseases. Our relatively poor understanding of the functions of non-coding genomic sequence, and the slow and laborious process of experimental validation of the functional significance of human regulatory variants, limits our ability to fully benefit from this information in our efforts to comprehend human disease. Humanized mouse models (HuMMs, in which human genes are introduced into the mouse, suggest an approach to this problem. In the past, HuMMs have been used successfully to study human disease variants; e.g., the complex genetic condition arising from Down syndrome, common monogenic disorders such as Huntington disease and β-thalassemia, and cancer susceptibility genes such as BRCA1. In this commentary, we highlight a novel method for high-throughput single-copy site-specific generation of HuMMs entitled High-throughput Human Genes on the X Chromosome (HuGX. This method can be applied to most human genes for which a bacterial artificial chromosome (BAC construct can be derived and a mouse-null allele exists. This strategy comprises (1 the use of recombineering technology to create a human variant-harbouring BAC, (2 knock-in of this BAC into the mouse genome using Hprt docking technology, and (3 allele comparison by interspecies complementation. We demonstrate the throughput of the HuGX method by generating a series of seven different alleles for the human NR2E1 gene at Hprt. In future challenges, we consider the current limitations of experimental approaches and call for a concerted effort by the genetics community, for both human and mouse, to solve the challenge of the functional analysis of human regulatory variation.

  1. Progress in functional genomics of drug-producing microorganisms%微生物药物产生菌功能基因组学研究进展

    Institute of Scientific and Technical Information of China (English)

    吴杭; 白林泉; 周秀芬; 邓子新

    2013-01-01

    Microbial drugs are secondary metabolites with diverse structures and bioactivities. In recent years, considerable genomes of the drug-producing microorganisms have been completely sequenced. Subsequently, functional genomic studies have been performed, which shed new lights on anibiotic biosynthesis, morphological differentiation, regulation, phylogeny and evolution, and genome mining of secondary metabolism. Herein, functional genomics for four important antibiotic producers is discussed, focusing on the genetic basis for penicillin overproduction, genomic and transcriptomic analysis of erythromycin-producing Saccharopolyspora erythraea, A-factor regulatory networks of streptomycin-producing Streptomyces griseus, construction of surrogate host for the heterologous expression of secondary metabolites and high-yielding strain of Streptomyces avermitilis, and genome mining for novel natural products. Moreover, current status on genomics of drug-producing microorganisms in China is summarized, and the perspective of genomic studies is predicted at both the basic research and the applied science aspects.%微生物药物是一类化学结构和生物活性多样的次级代谢产物,近年来其多个产生菌基因组序列已经被测定完成,在此基础上开展的功能基因组研究方兴未艾,并在抗生素生物合成、形态分化、调控、系统发育与进化以及次级代谢产物挖掘等方面有着新的发现,展现出广阔的研究前景.本文重点阐述了四种重要抗生素产生菌功能基因组学的研究现状,集中于青霉素高产的遗传机制、红霉素产生菌红色糖多孢菌基因组与转录组分析、链霉素产生菌灰色链霉菌中A因子调控网络、阿维菌素产生菌作为次级代谢物异源表达的通用宿主与超高产菌株构建以及新型天然产物的挖掘等研究内容,同时简要介绍了当前我国微生物药物产生菌基因组学的研究概况,并从基础与应用两个角度对

  2. Genome-wide population-based association study of extremely overweight young adults--the GOYA study

    DEFF Research Database (Denmark)

    Paternoster, Lavinia; Evans, David M; Nøhr, Ellen Aagaard

    2011-01-01

    Thirty-two common variants associated with body mass index (BMI) have been identified in genome-wide association studies, explaining ∼1.45% of BMI variation in general population cohorts. We performed a genome-wide association study in a sample of young adults enriched for extremely overweight...

  3. Genome-wide association study of colorectal cancer in Hispanics

    Science.gov (United States)

    Schmit, Stephanie L.; Schumacher, Fredrick R.; Edlund, Christopher K.; Conti, David V.; Ihenacho, Ugonna; Wan, Peggy; Van Den Berg, David; Casey, Graham; Fortini, Barbara K.; Lenz, Heinz-Josef; Tusié-Luna, Teresa; Aguilar-Salinas, Carlos A.; Moreno-Macías, Hortensia; Huerta-Chagoya, Alicia; Ordóñez-Sánchez, María Luisa; Rodríguez-Guillén, Rosario; Cruz-Bautista, Ivette; Rodríguez-Torres, Maribel; Muñóz-Hernández, Linda Liliana; Arellano-Campos, Olimpia; Gómez, Donají; Alvirde, Ulices; González-Villalpando, Clicerio; González-Villalpando, María Elena; Le Marchand, Loic; Haiman, Christopher A.; Figueiredo, Jane C.

    2016-01-01

    Genome-wide association studies (GWAS) have identified 58 susceptibility alleles across 37 regions associated with the risk of colorectal cancer (CRC) with P < 5×10−8. Most studies have been conducted in non-Hispanic whites and East Asians; however, the generalizability of these findings and the potential for ethnic-specific risk variation in Hispanic and Latino (HL) individuals have been largely understudied. We describe the first GWAS of common genetic variation contributing to CRC risk in HL (1611 CRC cases and 4330 controls). We also examine known susceptibility alleles and implement imputation-based fine-mapping to identify potential ethnicity-specific association signals in known risk regions. We discovered 17 variants across 4 independent regions that merit further investigation due to suggestive CRC associations (P < 1×10−6) at 1p34.3 (rs7528276; Odds Ratio (OR) = 1.86 [95% confidence interval (CI): 1.47–2.36); P = 2.5×10−7], 2q23.3 (rs1367374; OR = 1.37 (95% CI: 1.21–1.55); P = 4.0×10−7), 14q24.2 (rs143046984; OR = 1.65 (95% CI: 1.36–2.01); P = 4.1×10−7) and 16q12.2 [rs142319636; OR = 1.69 (95% CI: 1.37–2.08); P=7.8×10−7]. Among the 57 previously published CRC susceptibility alleles with minor allele frequency ≥1%, 76.5% of SNPs had a consistent direction of effect and 19 (33.3%) were nominally statistically significant (P < 0.05). Further, rs185423955 and rs60892987 were identified as novel secondary susceptibility variants at 3q26.2 (P = 5.3×10–5) and 11q12.2 (P = 6.8×10−5), respectively. Our findings demonstrate the importance of fine mapping in HL. These results are informative for variant prioritization in functional studies and future risk prediction modeling in minority populations. PMID:27207650

  4. Novel Progress in One-Dimensional Carbon Nanotubes Studies

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ One-dimensional carbon nanotubes (CNT) have received considerable attention from researchers worldwide. It is not only because of their unique physical properties, but also their potential applications. Recently, researchers of the CAS Institute of Physics have made new progress in the field.

  5. Studies on GaN-based laser devices make progress

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ A research team led by YANG Hui and CHEN Lianghui with the CAS Institute of Semiconductors (ISCAS) has made breakthrough progress in addressing key technological problems for the GaN-based laser diodes development. The research results were spoken highly at a panel meeting of experts held on 26 November, 2007 in Beijing.

  6. Recent progress of fuel layering study for FIREX cryogenic target

    Directory of Open Access Journals (Sweden)

    Iwamoto A.

    2013-11-01

    Full Text Available The collaboration research of ILE and NIFS has made progress on the FIREX target developments. We have two fuel layering strategies: a foam shell method and a conical laser guide heating technique. To date, preliminary and principle demonstration stages on both fuel layering methods have been reached. This paper describes the present status of the target developments.

  7. Progression from Sustained BK Viruria to Sustained BK Viremia with Immunosuppression Reduction Is Not Associated with Changes in the Noncoding Control Region of the BK Virus Genome

    Science.gov (United States)

    Memon, Imran A.; Parikh, Bijal A.; Gaudreault-Keener, Monique; Skelton, Rebecca; Storch, Gregory A.; Brennan, Daniel C.

    2012-01-01

    Changes in the BK virus archetypal noncoding control region (NCCR) have been associated with BK-virus-associated nephropathy (BKVAN). Whether sustained viremia, a surrogate for BKVAN, is associated with significant changes in the BK-NCCR is unknown. We performed PCR amplification and sequencing of (1) stored urine and (2) plasma samples from the time of peak viremia from 11 patients with sustained viremia who participated in a 200-patient clinical trial. The antimetabolite was withdrawn for BK viremia and reduction of the calcineurin inhibitor for sustained BK viremia. DNA sequencing from the 11 patients with sustained viremia revealed 8 insertions, 16 transversions, 3 deletions, and 17 transitions. None were deemed significant. No patient developed clinically evident BKVAN. Our data support, at a genomic level, the effectiveness of reduction of immunosuppression for prevention of progression from viremia to BKVAN. PMID:22701777

  8. Genome-wide association study of pancreatic cancer in Japanese population.

    Directory of Open Access Journals (Sweden)

    Siew-Kee Low

    Full Text Available Pancreatic cancer shows very poor prognosis and is the fifth leading cause of cancer death in Japan. Previous studies indicated some genetic factors contributing to the development and progression of pancreatic cancer; however, there are limited reports for common genetic variants to be associated with this disease, especially in the Asian population. We have conducted a genome-wide association study (GWAS using 991 invasive pancreatic ductal adenocarcinoma cases and 5,209 controls, and identified three loci showing significant association (P-value<5x10(-7 with susceptibility to pancreatic cancer. The SNPs that showed significant association carried estimated odds ratios of 1.29, 1.32, and 3.73 with 95% confidence intervals of 1.17-1.43, 1.19-1.47, and 2.24-6.21; P-value of 3.30x10(-7, 3.30x10(-7, and 4.41x10(-7; located on chromosomes 6p25.3, 12p11.21 and 7q36.2, respectively. These associated SNPs are located within linkage disequilibrium blocks containing genes that have been implicated some roles in the oncogenesis of pancreatic cancer.

  9. Glaucoma Monitoring in a Clinical Setting Glaucoma Progression Analysis vs Nonparametric Progression Analysis in the Groningen Longitudinal Glaucoma Study

    NARCIS (Netherlands)

    Wesselink, Christiaan; Heeg, Govert P.; Jansonius, Nomdo M.

    Objective: To compare prospectively 2 perimetric progression detection algorithms for glaucoma, the Early Manifest Glaucoma Trial algorithm (glaucoma progression analysis [GPA]) and a nonparametric algorithm applied to the mean deviation (MD) (nonparametric progression analysis [NPA]). Methods:

  10. Integrated Genome-Based Studies of Shewanella Echophysiology

    Energy Technology Data Exchange (ETDEWEB)

    Margrethe H. Serres

    2012-06-29

    Shewanella oneidensis MR-1 is a motile, facultative {gamma}-Proteobacterium with remarkable respiratory versatility; it can utilize a range of organic and inorganic compounds as terminal electronacceptors for anaerobic metabolism. The ability to effectively reduce nitrate, S0, polyvalent metals andradionuclides has established MR-1 as an important model dissimilatory metal-reducing microorganism for genome-based investigations of biogeochemical transformation of metals and radionuclides that are of concern to the U.S. Department of Energy (DOE) sites nationwide. Metal-reducing bacteria such as Shewanella also have a highly developed capacity for extracellular transfer of respiratory electrons to solid phase Fe and Mn oxides as well as directly to anode surfaces in microbial fuel cells. More broadly, Shewanellae are recognized free-living microorganisms and members of microbial communities involved in the decomposition of organic matter and the cycling of elements in aquatic and sedimentary systems. To function and compete in environments that are subject to spatial and temporal environmental change, Shewanella must be able to sense and respond to such changes and therefore require relatively robust sensing and regulation systems. The overall goal of this project is to apply the tools of genomics, leveraging the availability of genome sequence for 18 additional strains of Shewanella, to better understand the ecophysiology and speciation of respiratory-versatile members of this important genus. To understand these systems we propose to use genome-based approaches to investigate Shewanella as a system of integrated networks; first describing key cellular subsystems - those involved in signal transduction, regulation, and metabolism - then building towards understanding the function of whole cells and, eventually, cells within populations. As a general approach, this project will employ complimentary "top-down" - bioinformatics-based genome functional predictions, high

  11. HuGE Watch: tracking trends and patterns of published studies of genetic association and human genome epidemiology in near-real time.

    Science.gov (United States)

    Yu, Wei; Wulf, Anja; Yesupriya, Ajay; Clyne, Melinda; Khoury, Muin Joseph; Gwinn, Marta

    2008-09-01

    HuGE Watch is a web-based application for tracking the evolution of published studies on genetic association and human genome epidemiology in near-real time. The application allows users to display temporal trends and spatial distributions as line charts and google maps, providing a quick overview of progress in the field. http://www.hugenavigator.net/HuGENavigator/startPageWatch.do

  12. Integrated Genome-Based Studies of Shewanella Ecophysiology

    Energy Technology Data Exchange (ETDEWEB)

    Andrei L. Osterman, Ph.D.

    2012-12-17

    Integration of bioinformatics and experimental techniques was applied to mapping and characterization of the key components (pathways, enzymes, transporters, regulators) of the core metabolic machinery in Shewanella oneidensis and related species with main focus was on metabolic and regulatory pathways involved in utilization of various carbon and energy sources. Among the main accomplishments reflected in ten joint publications with other participants of Shewanella Federation are: (i) A systems-level reconstruction of carbohydrate utilization pathways in the genus of Shewanella (19 species). This analysis yielded reconstruction of 18 sugar utilization pathways including 10 novel pathway variants and prediction of > 60 novel protein families of enzymes, transporters and regulators involved in these pathways. Selected functional predictions were verified by focused biochemical and genetic experiments. Observed growth phenotypes were consistent with bioinformatic predictions providing strong validation of the technology and (ii) Global genomic reconstruction of transcriptional regulons in 16 Shewanella genomes. The inferred regulatory network includes 82 transcription factors, 8 riboswitches and 6 translational attenuators. Of those, 45 regulons were inferred directly from the genome context analysis, whereas others were propagated from previously characterized regulons in other species. Selected regulatory predictions were experimentally tested. Integration of this analysis with microarray data revealed overall consistency and provided additional layer of interactions between regulons. All the results were captured in the new database RegPrecise, which is a joint development with the LBNL team. A more detailed analysis of the individual subsystems, pathways and regulons in Shewanella spp included bioinfiormatics-based prediction and experimental characterization of: (i) N-Acetylglucosamine catabolic pathway; (ii)Lactate utilization machinery; (iii) Novel Nrt

  13. Whole-exome/genome sequencing and genomics.

    Science.gov (United States)

    Grody, Wayne W; Thompson, Barry H; Hudgins, Louanne

    2013-12-01

    As medical genetics has progressed from a descriptive entity to one focused on the functional relationship between genes and clinical disorders, emphasis has been placed on genomics. Genomics, a subelement of genetics, is the study of the genome, the sum total of all the genes of an organism. The human genome, which is contained in the 23 pairs of nuclear chromosomes and in the mitochondrial DNA of each cell, comprises >6 billion nucleotides of genetic code. There are some 23,000 protein-coding genes, a surprisingly small fraction of the total genetic material, with the remainder composed of noncoding DNA, regulatory sequences, and introns. The Human Genome Project, launched in 1990, produced a draft of the genome in 2001 and then a finished sequence in 2003, on the 50th anniversary of the initial publication of Watson and Crick's paper on the double-helical structure of DNA. Since then, this mass of genetic information has been translated at an ever-increasing pace into useable knowledge applicable to clinical medicine. The recent advent of massively parallel DNA sequencing (also known as shotgun, high-throughput, and next-generation sequencing) has brought whole-genome analysis into the clinic for the first time, and most of the current applications are directed at children with congenital conditions that are undiagnosable by using standard genetic tests for single-gene disorders. Thus, pediatricians must become familiar with this technology, what it can and cannot offer, and its technical and ethical challenges. Here, we address the concepts of human genomic analysis and its clinical applicability for primary care providers.

  14. SARS-CoV Genome Polymorphism: A Bioinformatics Study

    Institute of Scientific and Technical Information of China (English)

    Gordana M. Pavlovi(c)-Lazeti(c); Nenad S. Miti(c); Andrija M. Tomovi(c); Mirjana D. Pavlovi(c); Milo(s) V.Beljanski

    2005-01-01

    A dataset of 103 SARS-CoV isolates (101 human patients and 2 palm civets) was investigated on different aspects of genome polymorphism and isolate classification.The number and the distribution of single nucleotide variations (SNVs) and insertions and deletions, with respect to a "profile", were determined and discussed ("profile" being a sequence containing the most represented letter per position).Distribution of substitution categories per codon positions, as well as synonymous and non-synonymous substitutions in coding regions of annotated isolates, was determined, along with amino acid (a.a.) property changes. Similar analysis was performed for the spike (S) protein in all the isolates (55 of them being predicted for the first time). The ratio Ka/Ks confirmed that the S gene was subjected to the Darwinian selection during virus transmission from animals to humans. Isolates from the dataset were classified according to genome polymorphism and genotypes. Genome polymorphism yields to two groups, one with a small number of SNVs and another with a large number of SNVs, with up to four subgroups with respect to insertions and deletions. We identified three basic nine-locus genotypes:TTTT/TTCGG, CGCC/TTCAT, and TGCC/TTCGT, with four subgenotypes.Both classifications proposed are in accordance with the new insights into possible epidemiological spread, both in space and time.

  15. Study of intrachromosomal duplications among the eukaryote genomes.

    Science.gov (United States)

    Achaz, G; Netter, P; Coissac, E

    2001-12-01

    Complete eukaryote chromosomes were investigated for intrachromosomal duplications of nucleotide sequences. The analysis was performed by looking for nonexact repeats on two complete genomes, Saccharomyces cerevisiae and Caenorhabditis elegans, and four partial ones, Drosophila melanogaster, Plasmodium falciparum, Arabidopsis thaliana, and Homo sapiens. Through this analysis, we show that all eukaryote chromosomes exhibit similar characteristics for their intrachromosomal repeats, suggesting similar dynamics: many direct repeats have their two copies physically close together, and these close direct repeats are more similar and shorter than the other repeats. On the contrary, there are almost no close inverted repeats. These results support a model for the dynamics of duplication. This model is based on a continuous genesis of tandem repeats and implies that most of the distant and inverted repeats originate from these tandem repeats by further chromosomal rearrangements (insertions, inversions, and deletions). Remnants of these predicted rearrangements have been brought out through fine analysis of the chromosome sequence. Despite these dynamics, shared by all eukaryotes, each genome exhibits its own style of intrachromosomal duplication: the density of repeated elements is similar in all chromosomes issued from the same genome, but is different between species. This density was further related to the relative rates of duplication, deletion, and mutation proper to each species. One should notice that the density of repeats in the X chromosome of C. elegans is much lower than in the autosomes of that organism, suggesting that the exchange between homologous chromosomes is important in the duplication process.

  16. Progressive Failure Studies of Composite Panels with and without Cutouts

    Science.gov (United States)

    Jaunky, Navin; Ambur, Damodar R.; Davila, Carlos G.; Hilburger, Mark; Bushnell, Dennis M. (Technical Monitor)

    2001-01-01

    Progressive failure analyses results are presented for composite panels with and without a cutout and subjected to in-plane shear loading and compression loading well into their postbuckling regime. Ply damage modes such as matrix cracking, fiber-matrix shear, and fiber failure are modeled by degrading the material properties. Results from finite element analyses are compared with experimental data. Good agreement between experimental data and numerical results are observed for most structural configurations when initial geometric imperfections are appropriately modeled.

  17. Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study

    Science.gov (United States)

    de Vries, Paul S.; Sabater-Lleal, Maria; Chasman, Daniel I.; Trompet, Stella; Kleber, Marcus E.; Chen, Ming-Huei; Wang, Jie Jin; Attia, John R.; Marioni, Riccardo E.; Weng, Lu-Chen; Grossmann, Vera; Brody, Jennifer A.; Venturini, Cristina; Tanaka, Toshiko; Rose, Lynda M.; Oldmeadow, Christopher; Mazur, Johanna; Basu, Saonli; Yang, Qiong; Ligthart, Symen; Hottenga, Jouke J.; Rumley, Ann; Mulas, Antonella; de Craen, Anton J. M.; Grotevendt, Anne; Taylor, Kent D.; Delgado, Graciela E.; Kifley, Annette; Lopez, Lorna M.; Berentzen, Tina L.; Mangino, Massimo; Bandinelli, Stefania; Morrison, Alanna C.; Hamsten, Anders; Tofler, Geoffrey; de Maat, Moniek P. M.; Draisma, Harmen H. M.; Lowe, Gordon D.; Zoledziewska, Magdalena; Sattar, Naveed; Lackner, Karl J.; Völker, Uwe; McKnight, Barbara; Huang, Jie; Holliday, Elizabeth G.; McEvoy, Mark A.; Starr, John M.; Hysi, Pirro G.; Hernandez, Dena G.; Guan, Weihua; Rivadeneira, Fernando; McArdle, Wendy L.; Slagboom, P. Eline; Zeller, Tanja; Psaty, Bruce M.; Uitterlinden, André G.; de Geus, Eco J. C.; Stott, David J.; Binder, Harald; Hofman, Albert; Franco, Oscar H.; Rotter, Jerome I.; Ferrucci, Luigi; Spector, Tim D.; Deary, Ian J.; März, Winfried; Greinacher, Andreas; Wild, Philipp S.; Cucca, Francesco; Boomsma, Dorret I.; Watkins, Hugh; Tang, Weihong; Ridker, Paul M.; Jukema, Jan W.; Scott, Rodney J.; Mitchell, Paul; Hansen, Torben; O'Donnell, Christopher J.; Smith, Nicholas L.; Strachan, David P.

    2017-01-01

    An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In order to assess the improvement of 1000G over HapMap imputation in identifying associated loci, we compared the results of GWA studies of circulating fibrinogen based on the two reference panels. Using both HapMap and 1000G imputation we performed a meta-analysis of 22 studies comprising the same 91,953 individuals. We identified six additional signals using 1000G imputation, while 29 loci were associated using both HapMap and 1000G imputation. One locus identified using HapMap imputation was not significant using 1000G imputation. The genome-wide significance threshold of 5×10−8 is based on the number of independent statistical tests using HapMap imputation, and 1000G imputation may lead to further independent tests that should be corrected for. When using a stricter Bonferroni correction for the 1000G GWA study (P-value < 2.5×10−8), the number of loci significant only using HapMap imputation increased to 4 while the number of loci significant only using 1000G decreased to 5. In conclusion, 1000G imputation enabled the identification of 20% more loci than HapMap imputation, although the advantage of 1000G imputation became less clear when a stricter Bonferroni correction was used. More generally, our results provide insights that are applicable to the implementation of other dense reference panels that are under development. PMID:28107422

  18. [Importance of modern genome-wide studies for the risk of myocardial infarction].

    Science.gov (United States)

    Kessler, T; Erdmann, J; Schunkert, H

    2014-02-01

    The individual genetic susceptibility is a cornerstone in the pathogenesis of coronary artery disease (CAD). The search for the genetic background and the subsequently altered molecular mechanisms has been ineffective for several years. The increase in genome-wide association studies in recent years has changed the scenario and more than 40 variants have so far been identified to be highly significantly associated with CAD and the risk of myocardial infarction (MI). Whereas most of these findings affect frequent polymorphisms, exome-wide sequencing in families with a high prevalence of CAD revealed mutations with a high penetrance and as a consequence a high risk of suffering from MI. The findings allow a deeper insight into functional mechanisms involved in the pathogenesis of atherosclerosis. Furthermore, the data enables validation of the numerous epidemiologically identified risk markers with respect to the causal role in the development of CAD, making the genetic architecture of CAD much more transparent. Nevertheless, individual risk prediction has only made weak progress in the face of the new findings. Every individual without exception carries numerous risk alleles even when the number and effect strength shows individual differences. Thus, a varying degree of genetic susceptibility is shared by all of us. Current research is therefore focusing on the functional integration of genetic information to discover new approaches to prevention and therapy.

  19. Prediction of disease and phenotype associations from genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Stephanie N Lewis

    Full Text Available BACKGROUND: Genome wide association studies (GWAS have proven useful as a method for identifying genetic variations associated with diseases. In this study, we analyzed GWAS data for 61 diseases and phenotypes to elucidate common associations based on single nucleotide polymorphisms (SNP. The study was an expansion on a previous study on identifying disease associations via data from a single GWAS on seven diseases. METHODOLOGY/PRINCIPAL FINDINGS: Adjustments to the originally reported study included expansion of the SNP dataset using Linkage Disequilibrium (LD and refinement of the four levels of analysis to encompass SNP, SNP block, gene, and pathway level comparisons. A pair-wise comparison between diseases and phenotypes was performed at each level and the Jaccard similarity index was used to measure the degree of association between two diseases/phenotypes. Disease relatedness networks (DRNs were used to visualize our results. We saw predominant relatedness between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis for the first three levels of analysis. Expected relatedness was also seen between lipid- and blood-related traits. CONCLUSIONS/SIGNIFICANCE: The predominant associations between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis can be validated by clinical studies. The diseases have been proposed to share a systemic inflammation phenotype that can result in progression of additional diseases in patients with one of these three diseases. We also noticed unexpected relationships between metabolic and neurological diseases at the pathway comparison level. The less significant relationships found between diseases require a more detailed literature review to determine validity of the predictions. The results from this study serve as a first step towards a better understanding of seemingly unrelated diseases and phenotypes with similar symptoms or modes of treatment.

  20. Progress in spondylarthritis. Progress in studies of the genetics of ankylosing spondylitis.

    Science.gov (United States)

    Brown, Matthew A

    2009-01-01

    The advent of high-throughput SNP genotyping methods has advanced research into the genetics of common complex genetic diseases such as ankylosing spondylitis (AS) rapidly in recent times. The identification of associations with the genes IL23R and ERAP1 have been robustly replicated, and advances have been made in studies of the major histocompatibility complex genetics of AS, and of KIR gene variants and the disease. The findings are already being translated into increased understanding of the immunological pathways involved in AS, and raising novel potential therapies. The current studies in AS remain underpowered, and no full genomewide association study has yet been reported in AS; such studies are likely to add to the significant advances that have already been made.

  1. Dissecting inflammatory complications in critically injured patients by within-patient gene expression changes: a longitudinal clinical genomics study.

    Directory of Open Access Journals (Sweden)

    Keyur H Desai

    2011-09-01

    Full Text Available BACKGROUND: Trauma is the number one killer of individuals 1-44 y of age in the United States. The prognosis and treatment of inflammatory complications in critically injured patients continue to be challenging, with a history of failed clinical trials and poorly understood biology. New approaches are therefore needed to improve our ability to diagnose and treat this clinical condition. METHODS AND FINDINGS: We conducted a large-scale study on 168 blunt-force trauma patients over 28 d, measuring ∼400 clinical variables and longitudinally profiling leukocyte gene expression with ∼800 microarrays. Marshall MOF (multiple organ failure clinical score trajectories were first utilized to organize the patients into five categories of increasingly poor outcomes. We then developed an analysis framework modeling early within-patient expression changes to produce a robust characterization of the genomic response to trauma. A quarter of the genome shows early expression changes associated with longer-term post-injury complications, captured by at least five dynamic co-expression modules of functionally related genes. In particular, early down-regulation of MHC-class II genes and up-regulation of p38 MAPK signaling pathway were found to strongly associate with longer-term post-injury complications, providing discrimination among patient outcomes from expression changes during the 40-80 h window post-injury. CONCLUSIONS: The genomic characterization provided here substantially expands the scope by which the molecular response to trauma may be characterized and understood. These results may be instrumental in furthering our understanding of the disease process and identifying potential targets for therapeutic intervention. Additionally, the quantitative approach we have introduced is potentially applicable to future genomics studies of rapidly progressing clinical conditions. TRIAL REGISTRATION: ClinicalTrials.gov NCT00257231

  2. Genome-wide association studies of female reproduction in tropically adapted beef cattle

    National Research Council Canada - National Science Library

    Hawken, R J; Zhang, Y D; Fortes, M R S; Collis, E; Barris, W C; Corbet, N J; Williams, P J; Fordyce, G; Holroyd, R G; Walkley, J R W; Barendse, W; Johnston, D J; Prayaga, K C; Tier, B; Reverter, A; Lehnert, S A

    2012-01-01

    .... To elucidate the genetics underlying reproduction in beef cattle, we performed a genome-wide association study using the bovine SNP50 chip in 2 tropically adapted beef cattle breeds, Brahman and Tropical Composite...

  3. Integrating cytogenetics and genomics in comparative evolutionary studies of cichlid fish

    Directory of Open Access Journals (Sweden)

    Mazzuchelli Juliana

    2012-09-01

    Full Text Available Abstract Background The availability of a large number of recently sequenced vertebrate genomes opens new avenues to integrate cytogenetics and genomics in comparative and evolutionary studies. Cytogenetic mapping can offer alternative means to identify conserved synteny shared by distinct genomes and also to define genome regions that are still not fine characterized even after wide-ranging nucleotide sequence efforts. An efficient way to perform comparative cytogenetic mapping is based on BAC clones mapping by fluorescence in situ hybridization. In this report, to address the knowledge gap on the genome evolution in cichlid fishes, BAC clones of an Oreochromis niloticus library covering the linkage groups (LG 1, 3, 5, and 7 were mapped onto the chromosomes of 9 African cichlid species. The cytogenetic mapping data were also integrated with BAC-end sequences information of O. niloticus and comparatively analyzed against the genome of other fish species and vertebrates. Results The location of BACs from LG1, 3, 5, and 7 revealed a strong chromosomal conservation among the analyzed cichlid species genomes, which evidenced a synteny of the markers of each LG. Comparative in silico analysis also identified large genomic blocks that were conserved in distantly related fish groups and also in other vertebrates. Conclusions Although it has been suggested that fishes contain plastic genomes with high rates of chromosomal rearrangements and probably low rates of synteny conservation, our results evidence that large syntenic chromosome segments have been maintained conserved during evolution, at least for the considered markers. Additionally, our current cytogenetic mapping efforts integrated with genomic approaches conduct to a new perspective to address important questions involving chromosome evolution in fishes.

  4. A Genome-Wide Association Study for Regulators of Micronucleus Formation in Mice

    Directory of Open Access Journals (Sweden)

    Rebecca E. McIntyre

    2016-08-01

    Full Text Available In mammals the regulation of genomic instability plays a key role in tumor suppression and also controls genome plasticity, which is important for recombination during the processes of immunity and meiosis. Most studies to identify regulators of genomic instability have been performed in cells in culture or in systems that report on gross rearrangements of the genome, yet subtle differences in the level of genomic instability can contribute to whole organism phenotypes such as tumor predisposition. Here we performed a genome-wide association study in a population of 1379 outbred Crl:CFW(SW-US_P08 mice to dissect the genetic landscape of micronucleus formation, a biomarker of chromosomal breaks, whole chromosome loss, and extranuclear DNA. Variation in micronucleus levels is a complex trait with a genome-wide heritability of 53.1%. We identify seven loci influencing micronucleus formation (false discovery rate <5%, and define candidate genes at each locus. Intriguingly at several loci we find evidence for sexual dimorphism in micronucleus formation, with a locus on chromosome 11 being specific to males.

  5. Genome-wide Association Study of Obsessive-Compulsive Disorder

    Science.gov (United States)

    Stewart, S Evelyn; Yu, Dongmei; Scharf, Jeremiah M; Neale, Benjamin M; Fagerness, Jesen A; Mathews, Carol A; Arnold, Paul D; Evans, Patrick D; Gamazon, Eric R; Osiecki, Lisa; McGrath, Lauren; Haddad, Stephen; Crane, Jacquelyn; Hezel, Dianne; Illman, Cornelia; Mayerfeld, Catherine; Konkashbaev, Anuar; Liu, Chunyu; Pluzhnikov, Anna; Tikhomirov, Anna; Edlund, Christopher K; Rauch, Scott L; Moessner, Rainald; Falkai, Peter; Maier, Wolfgang; Ruhrmann, Stephan; Grabe, Hans-Jörgen; Lennertz, Leonard; Wagner, Michael; Bellodi, Laura; Cavallini, Maria Cristina; Richter, Margaret A; Cook, Edwin H; Kennedy, James L; Rosenberg, David; Stein, Dan J; Hemmings, Sian MJ; Lochner, Christine; Azzam, Amin; Chavira, Denise A; Fournier, Eduardo; Garrido, Helena; Sheppard, Brooke; Umaña, Paul; Murphy, Dennis L; Wendland, Jens R; Veenstra-VanderWeele, Jeremy; Denys, Damiaan; Blom, Rianne; Deforce, Dieter; Van Nieuwerburgh, Filip; Westenberg, Herman GM; Walitza, Susanne; Egberts, Karin; Renner, Tobias; Miguel, Euripedes Constantino; Cappi, Carolina; Hounie, Ana G; Conceição do Rosário, Maria; Sampaio, Aline S; Vallada, Homero; Nicolini, Humberto; Lanzagorta, Nuria; Camarena, Beatriz; Delorme, Richard; Leboyer, Marion; Pato, Carlos N; Pato, Michele T; Voyiaziakis, Emanuel; Heutink, Peter; Cath, Danielle C; Posthuma, Danielle; Smit, Jan H; Samuels, Jack; Bienvenu, O Joseph; Cullen, Bernadette; Fyer, Abby J; Grados, Marco A; Greenberg, Benjamin D; McCracken, James T; Riddle, Mark A; Wang, Ying; Coric, Vladimir; Leckman, James F; Bloch, Michael; Pittenger, Christopher; Eapen, Valsamma; Black, Donald W; Ophoff, Roel A; Strengman, Eric; Cusi, Daniele; Turiel, Maurizio; Frau, Francesca; Macciardi, Fabio; Gibbs, J Raphael; Cookson, Mark R; Singleton, Andrew; Hardy, John; Crenshaw, Andrew T; Parkin, Melissa A; Mirel, Daniel B; Conti, David V; Purcell, Shaun; Nestadt, Gerald; Hanna, Gregory L; Jenike, Michael A; Knowles, James A; Cox, Nancy; Pauls, David L

    2014-01-01

    Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1,465 cases, 5,557 ancestry-matched controls and 400 complete trios remained, with a common set of 469,410 autosomal and 9,657 X-chromosome SNPs. Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two p-values were located within DLGAP1 (p=2.49×10-6 and p=3.44×10-6), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a p-value=3.84 × 10-8. However, when trios were meta-analyzed with the combined case-control samples, the p-value for this variant was 3.62×10-5, losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation-QTLs (p<0.001) and frontal lobe eQTLs (p=0.001) was observed within the top-ranked SNPs (p<0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD. PMID:22889921

  6. Progress study of the cardiac damage in Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    ZHANG Yao

    2013-05-01

    Full Text Available Duchenne muscular dystrophy (DMD is a fatal muscular disease with rapid progression in children. Most patients die of respiratory and circulatory failure before the age of 20 if there is no systematic treatment. Now the heart problem in this disease has become increasingly prominent, and is thought to be closely associated with certain dystrophin exon deletion. We would like to review the epidemiology, relevance of dystrophin, pathogenesis, clinical manifestations and pathological features, as well as early prevention and treatment of DMD.

  7. [Progress in gene therapy study of Leber congenital amaurosis].

    Science.gov (United States)

    Pan, Shan-Shan; Zheng, Qin-Xiang; Li, Wen-Sheng; Pang, Ji-Jing

    2011-01-01

    Leber congenital amaurosis (LCA) is an early onset retinal dystrophy that causes severe visual impairment. With the development of molecular genetics and the therapeutic gene replacement technology, the adeno-associated viral (AAV) vector-mediated gene therapy for LCA achieved encouraging progress in the past decade. The success of the Phase I clinical trials of human RPE65 gene therapy for LCA II patients makes it a pioneer in the field of retinal gene therapy and brings light to the cure of other hereditary retinopathy. This article briefly reviews the recent developments in the preclinical animal experiments and Phase I clinical trials for LCA.

  8. Nationwide Genomic Study in Denmark Reveals Remarkable Population Homogeneity

    DEFF Research Database (Denmark)

    Athanasiadis, Georgios; Cheng, Jade Y; Vilhjálmsson, Bjarni J;

    2016-01-01

    polygenic predictions of phenotypic traits in adolescents. We observed remarkable homogeneity across different geographic regions, although we could still detect weak signals of genetic structure reflecting the history of the country. Denmark presented genomic affinity with primarily neighboring countries...... with overall resemblance of decreasing weight from Britain, Sweden, Norway, Germany and France. A Polish admixture signal was detected in Zealand and Funen and our date estimates coincided with historical evidence of Wend settlements in the south of Denmark. We also observed considerably diverse demographic...

  9. Functional genomics in the study of yeast cell polarity: moving in the right direction.

    Science.gov (United States)

    Styles, Erin; Youn, Ji-Young; Mattiazzi Usaj, Mojca; Andrews, Brenda

    2013-01-01

    The budding yeast Saccharomyces cerevisiae has been used extensively for the study of cell polarity, owing to both its experimental tractability and the high conservation of cell polarity and other basic biological processes among eukaryotes. The budding yeast has also served as a pioneer model organism for virtually all genome-scale approaches, including functional genomics, which aims to define gene function and biological pathways systematically through the analysis of high-throughput experimental data. Here, we outline the contributions of functional genomics and high-throughput methodologies to the study of cell polarity in the budding yeast. We integrate data from published genetic screens that use a variety of functional genomics approaches to query different aspects of polarity. Our integrated dataset is enriched for polarity processes, as well as some processes that are not intrinsically linked to cell polarity, and may provide new areas for future study.

  10. Recent progress in the understanding of tissue culture-induced genome level changes in plants and potential applications.

    Science.gov (United States)

    Neelakandan, Anjanasree K; Wang, Kan

    2012-04-01

    In vitro cell and tissue-based systems have tremendous potential in fundamental research and for commercial applications such as clonal propagation, genetic engineering and production of valuable metabolites. Since the invention of plant cell and tissue culture techniques more than half a century ago, scientists have been trying to understand the morphological, physiological, biochemical and molecular changes associated with tissue culture responses. Establishment of de novo developmental cell fate in vitro is governed by factors such as genetic make-up, stress and plant growth regulators. In vitro culture is believed to destabilize the genetic and epigenetic program of intact plant tissue and can lead to chromosomal and DNA sequence variations, methylation changes, transposon activation, and generation of somaclonal variants. In this review, we discuss the current status of understanding the genomic and epigenomic changes that take place under in vitro conditions. It is hoped that a precise and comprehensive knowledge of the molecular basis of these variations and acquisition of developmental cell fate would help to devise strategies to improve the totipotency and embryogenic capability in recalcitrant species and genotypes, and to address bottlenecks associated with clonal propagation.

  11. Integrated genome-based studies of Shewanella ecophysiology

    Energy Technology Data Exchange (ETDEWEB)

    Segre Daniel; Beg Qasim

    2012-02-14

    This project was a component of the Shewanella Federation and, as such, contributed to the overall goal of applying the genomic tools to better understand eco-physiology and speciation of respiratory-versatile members of Shewanella genus. Our role at Boston University was to perform bioreactor and high throughput gene expression microarrays, and combine dynamic flux balance modeling with experimentally obtained transcriptional and gene expression datasets from different growth conditions. In the first part of project, we designed the S. oneidensis microarray probes for Affymetrix Inc. (based in California), then we identified the pathways of carbon utilization in the metal-reducing marine bacterium Shewanella oneidensis MR-1, using our newly designed high-density oligonucleotide Affymetrix microarray on Shewanella cells grown with various carbon sources. Next, using a combination of experimental and computational approaches, we built algorithm and methods to integrate the transcriptional and metabolic regulatory networks of S. oneidensis. Specifically, we combined mRNA microarray and metabolite measurements with statistical inference and dynamic flux balance analysis (dFBA) to study the transcriptional response of S. oneidensis MR-1 as it passes through exponential, stationary, and transition phases. By measuring time-dependent mRNA expression levels during batch growth of S. oneidensis MR-1 under two radically different nutrient compositions (minimal lactate and nutritionally rich LB medium), we obtain detailed snapshots of the regulatory strategies used by this bacterium to cope with gradually changing nutrient availability. In addition to traditional clustering, which provides a first indication of major regulatory trends and transcription factors activities, we developed and implemented a new computational approach for Dynamic Detection of Transcriptional Triggers (D2T2). This new method allows us to infer a putative topology of transcriptional dependencies

  12. Genome-wide Association Study of Personality Traits in the Long Life Family Study

    Directory of Open Access Journals (Sweden)

    Harold T Bae

    2013-05-01

    Full Text Available Personality traits have been shown to be associated with longevity and healthy aging. In order to discover novel genetic modifiers associated with personality traits as related with longevity, we performed a genome-wide association study (GWAS on personality factors assessed by NEO-FFI in individuals enrolled in the Long Life Family Study (LLFS, a study of 583 families (N up to 4595 with clustering for longevity in the United States and Denmark. Three SNPs, in almost perfect LD, associated with agreeableness reached genome-wide significance (p<10-8 and replicated in an additional sample of 1279 LLFS subjects, although one (rs9650241 failed to replicate and the other two were not available in two independent replication cohorts, the Baltimore Longitudinal Study of Aging and the New England Centenarian Study. Based on 10,000,000 permutations, the empirical p-value of 2X10-7 was observed for the genome-wide significant SNPs. Seventeen SNPs that reached marginal statistical significance in the two previous GWASs (p-value < 10-4 and 10-5, were also marginally significantly associated in this study (p-value < 0.05, although none of the associations passed the Bonferroni correction. In addition, we tested age-by-SNP interactions and found some significant associations. Since scores of personality traits in LLFS subjects change in the oldest ages, and genetic factors outweigh environmental factors to achieve extreme ages, these age-by-SNP interactions could be a proxy for complex gene-gene interactions affecting personality traits and longevity.

  13. Genomics of Salmonella Species

    Science.gov (United States)

    Canals, Rocio; McClelland, Michael; Santiviago, Carlos A.; Andrews-Polymenis, Helene

    Progress in the study of Salmonella survival, colonization, and virulence has increased rapidly with the advent of complete genome sequencing and higher capacity assays for transcriptomic and proteomic analysis. Although many of these techniques have yet to be used to directly assay Salmonella growth on foods, these assays are currently in use to determine Salmonella factors necessary for growth in animal models including livestock animals and in in vitro conditions that mimic many different environments. As sequencing of the Salmonella genome and microarray analysis have revolutionized genomics and transcriptomics of salmonellae over the last decade, so are new high-throughput sequencing technologies currently accelerating the pace of our studies and allowing us to approach complex problems that were not previously experimentally tractable.

  14. Experimental Approaches to Study Genome Packaging of Influenza A Viruses

    Directory of Open Access Journals (Sweden)

    Catherine Isel

    2016-08-01

    Full Text Available The genome of influenza A viruses (IAV consists of eight single-stranded negative sense viral RNAs (vRNAs encapsidated into viral ribonucleoproteins (vRNPs. It is now well established that genome packaging (i.e., the incorporation of a set of eight distinct vRNPs into budding viral particles, follows a specific pathway guided by segment-specific cis-acting packaging signals on each vRNA. However, the precise nature and function of the packaging signals, and the mechanisms underlying the assembly of vRNPs into sub-bundles in the cytoplasm and their selective packaging at the viral budding site, remain largely unknown. Here, we review the diverse and complementary methods currently being used to elucidate these aspects of the viral cycle. They range from conventional and competitive reverse genetics, single molecule imaging of vRNPs by fluorescence in situ hybridization (FISH and high-resolution electron microscopy and tomography of budding viral particles, to solely in vitro approaches to investigate vRNA-vRNA interactions at the molecular level.

  15. Progression of Microstructural Degeneration in Progressive Supranuclear Palsy and Corticobasal Syndrome: A Longitudinal Diffusion Tensor Imaging Study.

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    Full Text Available Progressive supranuclear palsy (PSP and corticobasal syndrome (CBS are both 4 microtubule binding repeat tauopathy related disorders. Clinical trials need new biomarkers to assess the effectiveness of tau-directed therapies. This study investigated the regional distribution of longitudinal diffusion tensor imaging changes, measured by fractional anisotropy, radial and axial diffusivity over 6 months median interval, in 23 normal control subjects, 35 patients with PSP, and 25 patients with CBS. A mixed-effects framework was used to test longitudinal changes within and between groups. Correlations between changes in diffusion variables and clinical progression were also tested. The study found that over a 6 month period and compared to controls, the most prominent changes in PSP were up to 3±1% higher rates of FA reduction predominantly in superior cerebellar peduncles, and up to 18±6% higher rates of diffusivity increases in caudate nuclei. The most prominent changes in CBS compared to controls were up to 4±1% higher rates of anisotropy reduction and 18±6% higher rates of diffusivity increase in basal ganglia and widespread white matter regions. Compared to PSP, CBS was mainly associated with up to 3±1% greater rates of anisotropy reduction around the central sulci, and 11±3% greater rates of diffusivity increase in superior fronto-occipital fascicules. Rates of diffusivity increases in the superior cerebellar peduncle correlated with rates of ocular motor decline in PSP patients. This study demonstrated that longitudinal diffusion tensor imaging measurement is a promising surrogate marker of disease progression in PSP and CBS over a relatively short period.

  16. Inflectional morphology in primary progressive aphasia: an elicited production study.

    Science.gov (United States)

    Wilson, Stephen M; Brandt, Temre H; Henry, Maya L; Babiak, Miranda; Ogar, Jennifer M; Salli, Chelsey; Wilson, Lisa; Peralta, Karen; Miller, Bruce L; Gorno-Tempini, Maria Luisa

    2014-09-01

    Inflectional morphology lies at the intersection of phonology, syntax and the lexicon, three language domains that are differentially impacted in the three main variants of primary progressive aphasia (PPA). To characterize spared and impaired aspects of inflectional morphology in PPA, we elicited inflectional morphemes in 48 individuals with PPA and 13 healthy age-matched controls. We varied the factors of regularity, frequency, word class, and lexicality, and used voxel-based morphometry to identify brain regions where atrophy was predictive of deficits on particular conditions. All three PPA variants showed deficits in inflectional morphology, with the specific nature of the deficits dependent on the anatomical and linguistic features of each variant. Deficits in inflecting low-frequency irregular words were associated with semantic PPA, with lexical/semantic deficits, and with left temporal atrophy. Deficits in inflecting pseudowords were associated with non-fluent/agrammatic and logopenic variants, with phonological deficits, and with left frontal and parietal atrophy.

  17. Progress on the europium neutron capture study using DANCE

    Science.gov (United States)

    Agvaanluvsan, U.; Becker, J. A.; Macri, R. A.; Parker, W.; Wilk, P.; Wu, C. Y.; Bredeweg, T. A.; Esch, E.; Haight, R. C.; O'Donnell, J. M.; Reifarth, R.; Rundberg, R. S.; Schwantes, J. M.; Ullmann, J. L.; Vieira, D. J.; Wilhelmy, J. B.; Wouters, J. M.; Mitchell, G. E.; Sheets, S.; Bečvář, F.; Krtička, M.

    2007-08-01

    The accurate measurement of neutron capture cross sections of the Eu isotopes is important for many reasons including nuclear astrophysics and nuclear diagnostics. Neutron capture excitation functions of 151,153Eu targets were measured recently using a 4π γ-ray calorimeter array DANCE located at the Los Alamos Neutron Science Center for En = 0.1-100 keV. The progress on the data analysis efforts is given in the present paper. The γ-ray multiplicity distributions for the Eu targets and Be backing are significantly different. The γ-ray multiplicity distribution is found to be the same for different neutron energies for both 151Eu and 153Eu. The statistical simulation to model the γ-ray decay cascade is summarized.

  18. Progress on the Europium Neutron-Capture Study using DANCE

    Energy Technology Data Exchange (ETDEWEB)

    Agvaanluvsan, U; Becker, J A; Macri, R A; Parker, W; Wilk, P; Wu, C Y; Bredeweg, T A; Esch, E; Haight, R C; O' Donnell, J M; Reifarth, R; Rundberg, R S; Schwantes, J M; Ullmann, J L; Vieira, D J; Wilhelmy, J B; Wouters, J M; Mitchell, G E; Sheets, S A; Becvar, F; Krticka, M

    2006-09-05

    The accurate measurement of neutron-capture cross sections of the Eu isotopes is important for many reasons including nuclear astrophysics and nuclear diagnostics. Neutron capture excitation functions of {sup 151,153}Eu targets were measured recently using a 4{pi} {gamma}-ray calorimeter array DANCE located at the Los Alamos Neutron Science Center for E{sub n} = 0.1-100 keV. The progress on the data analysis efforts is given in the present paper. The {gamma}-ray multiplicity distributions for the Eu targets and Be backing are significantly different. The {gamma}-ray multiplicity distribution is found to be the same for different neutron energies for both {sup 151}Eu and {sup 153}Eu. The statistical simulation to model the {gamma}-ray decay cascade is summarized.

  19. Progress on the europium neutron capture study using DANCE

    Energy Technology Data Exchange (ETDEWEB)

    Agvaanluvsan, U. [Lawrence Livermore National Laboratory, 7000 East Avenue, P.O. Box 808, L-414, Livermore, CA 94551 (United States)]. E-mail: agvaanluvsan1@llnl.gov; Becker, J.A. [Lawrence Livermore National Laboratory, 7000 East Avenue, P.O. Box 808, L-414, Livermore, CA 94551 (United States); Macri, R.A. [Lawrence Livermore National Laboratory, 7000 East Avenue, P.O. Box 808, L-414, Livermore, CA 94551 (United States); Parker, W. [Lawrence Livermore National Laboratory, 7000 East Avenue, P.O. Box 808, L-414, Livermore, CA 94551 (United States); Wilk, P. [Lawrence Livermore National Laboratory, 7000 East Avenue, P.O. Box 808, L-414, Livermore, CA 94551 (United States); Wu, C.Y. [Lawrence Livermore National Laboratory, 7000 East Avenue, P.O. Box 808, L-414, Livermore, CA 94551 (United States); Bredeweg, T.A.; Esch, E.; Haight, R.C.; O' Donnell, J.M.; Reifarth, R.; Rundberg, R.S.; Schwantes, J.M.; Ullmann, J.L.; Vieira, D.J.; Wilhelmy, J.B.; Wouters, J.M. [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Mitchell, G.E.; Sheets, S. [North Carolina State University, Raleigh, NC 27695 (United States)]|[Triangle Universities Nuclear Laboratory, Durham, NC 27708 (United States); Becvar, F.; Krticka, M. [Charles University in Prague, CZ 180 00 Prague 8 (Czech Republic)

    2007-08-15

    The accurate measurement of neutron capture cross sections of the Eu isotopes is important for many reasons including nuclear astrophysics and nuclear diagnostics. Neutron capture excitation functions of {sup 151,153}Eu targets were measured recently using a 4{pi} {gamma}-ray calorimeter array DANCE located at the Los Alamos Neutron Science Center for E {sub n} = 0.1-100 keV. The progress on the data analysis efforts is given in the present paper. The {gamma}-ray multiplicity distributions for the Eu targets and Be backing are significantly different. The {gamma}-ray multiplicity distribution is found to be the same for different neutron energies for both {sup 151}Eu and {sup 153}Eu. The statistical simulation to model the {gamma}-ray decay cascade is summarized.

  20. Comparative study of factor structure of Raven's Coloured Progressive Matrices.

    Science.gov (United States)

    Schmidtke, A; Schaller, S

    1980-12-01

    The Raven Coloured Progressive Matrices were administered on group or individual bases to children ranging in age from 4 yr. 9 mo. to 11 yr. 0 mo. (N = 728). Factor analysis yielded three factors: 1. Perceptual closure involving complex figures and patterns with heterogeneous inner structures, 2. Concrete and abstract reasoning, 3. Completion of homogeneous patterns and recognition of given elements. Factor matrix comparisons across age groups resulted in a mean similarity coefficient of .75. Comparisons of data with earlier analyses also resulted in high similarity. This supports the hypothesis of a three-factor structure rather than a four-factor solution or a simple dual classification into items which can be solved by perceptual processes and those which require conceptual solutions.

  1. Cost-effective cloud computing: a case study using the comparative genomics tool, roundup.

    Science.gov (United States)

    Kudtarkar, Parul; Deluca, Todd F; Fusaro, Vincent A; Tonellato, Peter J; Wall, Dennis P

    2010-12-22

    Comparative genomics resources, such as ortholog detection tools and repositories are rapidly increasing in scale and complexity. Cloud computing is an emerging technological paradigm that enables researchers to dynamically build a dedicated virtual cluster and may represent a valuable alternative for large computational tools in bioinformatics. In the present manuscript, we optimize the computation of a large-scale comparative genomics resource-Roundup-using cloud computing, describe the proper operating principles required to achieve computational efficiency on the cloud, and detail important procedures for improving cost-effectiveness to ensure maximal computation at minimal costs. Utilizing the comparative genomics tool, Roundup, as a case study, we computed orthologs among 902 fully sequenced genomes on Amazon's Elastic Compute Cloud. For managing the ortholog processes, we designed a strategy to deploy the web service, Elastic MapReduce, and maximize the use of the cloud while simultaneously minimizing costs. Specifically, we created a model to estimate cloud runtime based on the size and complexity of the genomes being compared that determines in advance the optimal order of the jobs to be submitted. We computed orthologous relationships for 245,323 genome-to-genome comparisons on Amazon's computing cloud, a computation that required just over 200 hours and cost $8,000 USD, at least 40% less than expected under a strategy in which genome comparisons were submitted to the cloud randomly with respect to runtime. Our cost savings projections were based on a model that not only demonstrates the optimal strategy for deploying RSD to the cloud, but also finds the optimal cluster size to minimize waste and maximize usage. Our cost-reduction model is readily adaptable for other comparative genomics tools and potentially of significant benefit to labs seeking to take advantage of the cloud as an alternative to local computing infrastructure.

  2. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma

    OpenAIRE

    Chambers, John C.; Zhang, Weihua; Sehmi, Joban; Li, Xinzhong; Wass, Mark N; Harst, Pim; Holm, Hilma; Sanna, Serena; Kavousi, Maryam; Baumeister, Sebastian E.; Coin, Lachlan J.; Deng, Guohong; Gieger, Christian; Heard-Costa, Nancy L.; Hottenga, Jouke-Jan

    2011-01-01

    Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, includi...

  3. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma

    OpenAIRE

    Chambers, John C.; Zhang, Weihua; Sehmi, Joban; Li, Xinzhong; Wass, Mark N; Harst, Pim; Holm, Hilma; Sanna, Serena; Kavousi, Maryam; Baumeister, Sebastian E.; Coin, Lachlan J.; Deng, Guohong; Gieger, Christian; Heard-Costa, Nancy L.; Hottenga, Jouke-Jan

    2011-01-01

    Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10−8 to P = 10−190). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including g...

  4. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.

    OpenAIRE

    Chambers, John C.; Zhang, Weihua; Sehmi, Joban; Li, Xinzhong; Wass, Mark N; Harst, Pim; Holm, Hilma; Sanna, Serena; Kavousi, Maryam; Baumeister, Sebastian E.; Coin, Lachlan J.; Abecasis, Goncalo R.; Ahmadi, Kourosh R; Boomsma, Dorret I; Caulfield, Mark

    2011-01-01

    Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, includi...

  5. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci

    OpenAIRE

    Stahl, Eli A; Raychaudhuri, Soumya; Remmers, Elaine F.; Xie, Gang; Eyre, Stephen; Thomson, Brian P.; Li, Yonghong; Kurreeman, Fina A. S.; Zhernakova, Alexandra; Hinks, Anne; Guiducci, Candace; Chen, Robert; Alfredsson, Lars; Amos, Christopher I.; Ardlie, Kristin G.

    2010-01-01

    To identify novel genetic risk factors for rheumatoid arthritis (RA), we conducted a genome-wide association study (GWAS) meta-analysis of 5,539 autoantibody positive RA cases and 20,169 controls of European descent, followed by replication in an independent set of 6,768 RA cases and 8,806 controls. Of 34 SNPs selected for replication, 7 novel RA risk alleles were identified at genome-wide significance (P

  6. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies

    DEFF Research Database (Denmark)

    Bulik-Sullivan, Brendan K.; Loh, Po-Ru; Finucane, Hilary K.

    2015-01-01

    Both polygenicity (many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from...... correction factor than genomic control. We find strong evidence that polygenicity accounts for the majority of the inflation in test statistics in many GWAS of large sample size....

  7. Progress and Prospect of Genomics Technologies in Horticultural Crops%园艺作物基因组技术研究及展望

    Institute of Scientific and Technical Information of China (English)

    王晓武

    2013-01-01

    China is the largest growing and consuming country of horticultural crops in the world. The second generation of sequencing technologies achieved significant breakthrough and greatly influenced improvement of horticultural crops. A number of important horticultural crops, including Chinese cabbage, cucumber, tomato, melon and water melon et al. have recently being sequenced. After analyzing the progress of the genomics technology and policies adopted by the major contrived in the world, the paper listed some major tasks for promoting genomics of horticultural crops in China and proposed some policy recommendations.%  我国是世界上园艺作物种植和消费大国。第二代基因组测序技术取得了重大突破,并对园艺作物改良产生了重大影响。近年来,完成了白菜、黄瓜、番茄、甜瓜和西瓜等一系列重要园艺作物的基因组测序。在分析了世界基因组前沿技术发展现状与方向和主要国家园艺作物基因组研究采取的主要政策的基础上,围绕园艺作物的发展,提出了我国发展园艺作物基因组技术重点任务和需要采取的政策措施。

  8. Genome-wide association study of metabolic traits reveals novel gene-metabolite-disease links.

    Directory of Open Access Journals (Sweden)

    Rico Rueedi

    2014-02-01

    Full Text Available Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on (1H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10(-8 and independent associations between single nucleotide polymorphisms (SNP and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10(-44 and lysine (rs8101881, P = 1.2×10(-33, respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers.

  9. Genome-Wide Association Study of Metabolic Traits Reveals Novel Gene-Metabolite-Disease Links

    Science.gov (United States)

    Nicholls, Andrew W.; Salek, Reza M.; Marques-Vidal, Pedro; Morya, Edgard; Sameshima, Koichi; Montoliu, Ivan; Da Silva, Laeticia; Collino, Sebastiano; Martin, François-Pierre; Rezzi, Serge; Steinbeck, Christoph; Waterworth, Dawn M.; Waeber, Gérard; Vollenweider, Peter; Beckmann, Jacques S.; Le Coutre, Johannes; Mooser, Vincent; Bergmann, Sven; Genick, Ulrich K.; Kutalik, Zoltán

    2014-01-01

    Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on 1H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10−8) and independent associations between single nucleotide polymorphisms (SNP) and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10−44) and lysine (rs8101881, P = 1.2×10−33), respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers. PMID:24586186

  10. Kodiak Island bald eagle migration and movements study: Progress report, update

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The purpose of this report is to update the progress of the bald eagle migration and movements study begun during July of 1982. The study objectives are: to...

  11. Kodiak Island bald eagle migration and movements study: Progress report update

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This report updates the progress of a bald eagle migration and movements study begun during July, 1982. The study objectives are: (1) to determine and compare...

  12. 1984 Pacific walrus harvest, health, and welfare study at Little Diomede Island, Alaska: Progress report

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This report is a progress update on the Pacific walrus harvest study that has been conducted in Diomede, Alaska in previous years. Study methods and results are...

  13. A hybrid approach for de novo human genome sequence assembly and phasing.

    Science.gov (United States)

    Mostovoy, Yulia; Levy-Sakin, Michal; Lam, Jessica; Lam, Ernest T; Hastie, Alex R; Marks, Patrick; Lee, Joyce; Chu, Catherine; Lin, Chin; Džakula, Željko; Cao, Han; Schlebusch, Stephen A; Giorda, Kristina; Schnall-Levin, Michael; Wall, Jeffrey D; Kwok, Pui-Yan

    2016-07-01

    Despite tremendous progress in genome sequencing, the basic goal of producing a phased (haplotype-resolved) genome sequence with end-to-end contiguity for each chromosome at reasonable cost and effort is still unrealized. In this study, we describe an approach to performing de novo genome assembly and experimental phasing by integrating the data from Illumina short-read sequencing, 10X Genomics linked-read sequencing, and BioNano Genomics genome mapping to yield a high-quality, phased, de novo assembled human genome.

  14. A brief summary of major advances in cotton functional genomics and molecular breeding studies in China

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Cotton fibers, commonly known as cotton lint, are single-celled trichomes derived from epidermal layers of cotton ovules. Despite of its importance in word trade, the molecular mechanisms of cotton fiber production is still poorly understood. Through transcriptome profiling, functional genomics, proteomics, metabolomics approaches as well as marker-assisted molecular breeding, scientists in China have made significant contributions in cotton research. Here, we briefly summarize major progresses made in Chinese laboratories, and discuss future directions and perspectives relative to the development of this unique crop plant.

  15. Evolution of a microbial nitrilase gene family: a comparative and environmental genomics study

    Directory of Open Access Journals (Sweden)

    Eads Jonathan R

    2005-08-01

    Full Text Available Abstract Background Completed genomes and environmental genomic sequences are bringing a significant contribution to understanding the evolution of gene families, microbial metabolism and community eco-physiology. Here, we used comparative genomics and phylogenetic analyses in conjunction with enzymatic data to probe the evolution and functions of a microbial nitrilase gene family. Nitrilases are relatively rare in bacterial genomes, their biological function being unclear. Results We examined the genetic neighborhood of the different subfamily genes and discovered conserved gene clusters or operons associated with specific nitrilase clades. The inferred evolutionary transitions that separate nitrilases which belong to different gene clusters correlated with changes in their enzymatic properties. We present evidence that Darwinian adaptation acted during one of those transitions and identified sites in the enzyme that may have been under positive selection. Conclusion Changes in the observed biochemical properties of the nitrilases associated with the different gene clusters are consistent with a hypothesis that those enzymes have been recruited to a novel metabolic pathway following gene duplication and neofunctionalization. These results demonstrate the benefits of combining environmental genomic sampling and completed genomes data with evolutionary and biochemical analyses in the study of gene families. They also open new directions for studying the functions of nitrilases and the genes they are associated with.

  16. Study on the Mitochondrial Genome of Sea Island Cotton (Gossypium barbadense) by BAC Library Screening

    Institute of Scientific and Technical Information of China (English)

    SU Ai-guo; LI Shuang-shuang; LIU Guo-zheng; LEI Bin-bin; KANG Ding-ming; LI Zhao-hu; MA Zhi-ying; HUA Jin-ping

    2014-01-01

    The plant mitochondrial genome displays complex features, particularly in terms of cytoplasmic male sterility (CMS). Therefore, research on the cotton mitochondrial genome may provide important information for analyzing genome evolution and exploring the molecular mechanism of CMS. In this paper, we present a preliminary study on the mitochondrial genome of sea island cotton (Gossypium barbadense) based on positive clones from the bacterial artiifcial chromosome (BAC) library. Thirty-ifve primers designed with the conserved sequences of functional genes and exons of mitochondria were used to screen positive clones in the genome library of the sea island cotton variety called Pima 90-53. Ten BAC clones were obtained and veriifed for further study. A contig was obtained based on six overlapping clones and subsequently laid out primarily on the mitochondrial genome. One BAC clone, clone 6 harbored with the inserter of approximate 115 kb mtDNA sequence, in which more than 10 primers fragments could be ampliifed, was sequenced and assembled using the Solexa strategy. Fifteen mitochondrial functional genes were revealed in clone 6 by gene annotation. The characteristics of the syntenic gene/exon of the sequences and RNA editing were preliminarily predicted.

  17. GStream: improving SNP and CNV coverage on genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Arnald Alonso

    Full Text Available We present GStream, a method that combines genome-wide SNP and CNV genotyping in the Illumina microarray platform with unprecedented accuracy. This new method outperforms previous well-established SNP genotyping software. More importantly, the CNV calling algorithm of GStream dramatically improves the results obtained by previous state-of-the-art methods and yields an accuracy that is close to that obtained by purely CNV-oriented technologies like Comparative Genomic Hybridization (CGH. We demonstrate the superior performance of GStream using microarray data generated from HapMap samples. Using the reference CNV calls generated by the 1000 Genomes Project (1KGP and well-known studies on whole genome CNV characterization based either on CGH or genotyping microarray technologies, we show that GStream can increase the number of reliably detected variants up to 25% compared to previously developed methods. Furthermore, the increased genome coverage provided by GStream allows the discovery of CNVs in close linkage disequilibrium with SNPs, previously associated with disease risk in published Genome-Wide Association Studies (GWAS. These results could provide important insights into the biological mechanism underlying the detected disease risk association. With GStream, large-scale GWAS will not only benefit from the combined genotyping of SNPs and CNVs at an unprecedented accuracy, but will also take advantage of the computational efficiency of the method.

  18. Whole genome association study of rheumatoid arthritis using 27 039 microsatellites.

    Science.gov (United States)

    Tamiya, Gen; Shinya, Minori; Imanishi, Tadashi; Ikuta, Tomoki; Makino, Satoshi; Okamoto, Koichi; Furugaki, Koh; Matsumoto, Toshiko; Mano, Shuhei; Ando, Satoshi; Nozaki, Yasuyuki; Yukawa, Wataru; Nakashige, Ryo; Yamaguchi, Daisuke; Ishibashi, Hideo; Yonekura, Manabu; Nakami, Yuu; Takayama, Seiken; Endo, Takaho; Saruwatari, Takuya; Yagura, Masaru; Yoshikawa, Yoko; Fujimoto, Kei; Oka, Akira; Chiku, Suenori; Linsen, Samuel E V; Giphart, Marius J; Kulski, Jerzy K; Fukazawa, Toru; Hashimoto, Hiroshi; Kimura, Minoru; Hoshina, Yuuichi; Suzuki, Yasuo; Hotta, Tomomitsu; Mochida, Joji; Minezaki, Takatoshi; Komai, Koichiro; Shiozawa, Shunichi; Taniguchi, Atsuo; Yamanaka, Hisashi; Kamatani, Naoyuki; Gojobori, Takashi; Bahram, Seiamak; Inoko, Hidetoshi

    2005-08-15

    A major goal of current human genome-wide studies is to identify the genetic basis of complex disorders. However, the availability of an unbiased, reliable, cost efficient and comprehensive methodology to analyze the entire genome for complex disease association is still largely lacking or problematic. Therefore, we have developed a practical and efficient strategy for whole genome association studies of complex diseases by charting the human genome at 100 kb intervals using a collection of 27,039 microsatellites and the DNA pooling method in three successive genomic screens of independent case-control populations. The final step in our methodology consists of fine mapping of the candidate susceptible DNA regions by single nucleotide polymorphisms (SNPs) analysis. This approach was validated upon application to rheumatoid arthritis, a destructive joint disease affecting up to 1% of the population. A total of 47 candidate regions were identified. The top seven loci, withstanding the most stringent statistical tests, were dissected down to individual genes and/or SNPs on four chromosomes, including the previously known 6p21.3-encoded Major Histocompatibility Complex gene, HLA-DRB1. Hence, microsatellite-based genome-wide association analysis complemented by end stage SNP typing provides a new tool for genetic dissection of multifactorial pathologies including common diseases.

  19. Frontotemporal dementia and its subtypes: a genome-wide association study

    Science.gov (United States)

    Ferrari, Raffaele; Hernandez, Dena G; Nalls, Michael A; Rohrer, Jonathan D; Ramasamy, Adaikalavan; Kwok, John B J; Dobson-Stone, Carol; Brooks, William S; Schofield, Peter R; Halliday, Glenda M; Hodges, John R; Piguet, Olivier; Bartley, Lauren; Thompson, Elizabeth; Haan, Eric; Hernández, Isabel; Ruiz, Agustín; Boada, Mercè; Borroni, Barbara; Padovani, Alessandro; Cruchaga, Carlos; Cairns, Nigel J; Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta; Forloni, Gianluigi; Galimberti, Daniela; Fenoglio, Chiara; Serpente, Maria; Scarpini, Elio; Clarimón, Jordi; Lleó, Alberto; Blesa, Rafael; Waldö, Maria Landqvist; Nilsson, Karin; Nilsson, Christer; Mackenzie, Ian R A; Hsiung, Ging-Yuek R; Mann, David M A; Grafman, Jordan; Morris, Christopher M; Attems, Johannes; Griffiths, Timothy D; McKeith, Ian G; Thomas, Alan J; Pietrini, P; Huey, Edward D; Wassermann, Eric M; Baborie, Atik; Jaros, Evelyn; Tierney, Michael C; Pastor, Pau; Razquin, Cristina; Ortega-Cubero, Sara; Alonso, Elena; Perneczky, Robert; Diehl-Schmid, Janine; Alexopoulos, Panagiotis; Kurz, Alexander; Rainero, Innocenzo; Rubino, Elisa; Pinessi, Lorenzo; Rogaeva, Ekaterina; George-Hyslop, Peter St; Rossi, Giacomina; Tagliavini, Fabrizio; Giaccone, Giorgio; Rowe, James B; Schlachetzki, J C M; Uphill, James; Collinge, John; Mead, S; Danek, Adrian; Van Deerlin, Vivianna M; Grossman, Murray; Trojanowsk, John Q; van der Zee, Julie; Deschamps, William; Van Langenhove, Tim; Cruts, Marc; Van Broeckhoven, Christine; Cappa, Stefano F; Le Ber, Isabelle; Hannequin, Didier; Golfier, Véronique; Vercelletto, Martine; Brice, Alexis; Nacmias, Benedetta; Sorbi, Sandro; Bagnoli, Silvia; Piaceri, Irene; Nielsen, Jørgen E; Hjermind, Lena E; Riemenschneider, Matthias; Mayhaus, Manuel; Ibach, Bernd; Gasparoni, Gilles; Pichler, Sabrina; Gu, Wei; Rossor, Martin N; Fox, Nick C; Warren, Jason D; Spillantini, Maria Grazia; Morris, Huw R; Rizzu, Patrizia; Heutink, Peter; Snowden, Julie S; Rollinson, Sara; Richardson, Anna; Gerhard, Alexander; Bruni, Amalia C; Maletta, Raffaele; Frangipane, Francesca; Cupidi, Chiara; Bernardi, Livia; Anfossi, Maria; Gallo, Maura; Conidi, Maria Elena; Smirne, Nicoletta; Rademakers, Rosa; Baker, Matt; Dickson, Dennis W; Graff-Radford, Neill R; Petersen, Ronald C; Knopman, David; Josephs, Keith A; Boeve, Bradley F; Parisi, Joseph E; Seeley, William W; Miller, Bruce L; Karydas, Anna M; Rosen, Howard; van Swieten, John C; Dopper, Elise G P; Seelaar, Harro; Pijnenburg, Yolande AL; Scheltens, Philip; Logroscino, Giancarlo; Capozzo, Rosa; Novelli, Valeria; Puca, Annibale A; Franceschi, M; Postiglione, Alfredo; Milan, Graziella; Sorrentino, Paolo; Kristiansen, Mark; Chiang, Huei-Hsin; Graff, Caroline; Pasquier, Florence; Rollin, Adeline; Deramecourt, Vincent; Lebert, Florence; Kapogiannis, Dimitrios; Ferrucci, Luigi; Pickering-Brown, Stuart; Singleton, Andrew B; Hardy, John; Momeni, Parastoo

    2014-01-01

    Summary Background Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes—MAPT, GRN, and C9orf72—have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402 healthy controls. All participants had European ancestry. In the discovery phase (samples from 2154 patients with FTD and 4308 controls), we did separate association analyses for each FTD subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10−8) and suggestive single-nucleotide polymorphisms. Findings We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10−8) that encompassed the HLA locus at 6p21.3 in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC, for the behavioural FTD subtype. Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation incis. Interpretation Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and possibly to shed light on the pathomechanisms contributing to FTD. Funding The National Institute of

  20. [Progress of anti-tumor study based on BRAF].

    Science.gov (United States)

    Yan, Gui-Rui; Xu, Zhi-Jian; Wang, He-Yao; Zhu, Wei-Liang

    2012-12-01

    BRAF is one of the most important pro-oncogenes, which is mutated in approximately 8% of human tumors. The most common BRAF mutation is a valine-to-glutamate transition (V600E) that is expressed primarily in melanoma, colorectal cancer and thyroid carcinoma. MEK/ERK is constitutively activated in the cells expressing BRAFV600E, leading to tumor development, invasion, and metastasis. Therefore, BRAFV600E is a therapeutic target for melanoma and some other BRAFV600E tumors. Vemurafenib, a BRAFV600E inhibitor, which was approved by FDA for the treatment of late-stage melanoma in 2011, produces improved rates of overall and progression-free survival in patients with the BRAFV600E mutation, making a dramatic breakthrough in melanoma treatment. Vemurafenib is also an individual target drug based on genetic diagnosis. However, its therapeutic success is limited by the emergence of drug resistance. Therefore, it is important to explore the mechanisms underlying the resistance for developing new inhibitor drugs and for preventing or delaying the resistance evolution to BRAF inhibitor drugs. In this review, we described the role of BRAFV600E as an anti-tumor drug target and the development of BRAF inhibitors. We also discussed the mechanisms leading to resistance of BRAFV600E inhibitors. Furthermore, therapeutic strategies that might be employed to overcome acquired resistance were proposed.

  1. Genome-wide association studies in nephrology: using known associations for data checks.

    Science.gov (United States)

    Wuttke, Matthias; Schaefer, Franz; Wong, Craig S; Köttgen, Anna

    2015-02-01

    Prior to conducting genome-wide association studies (GWAS) of renal traits and diseases, systematic checks to ensure data integrity and analytical work flow should be conducted. Using positive controls (ie, known associations between a single-nucleotide polymorphism [SNP] and a corresponding trait) allows for identifying errors that are not apparent solely from global evaluation of summary statistics. Strong genetic control associations of chronic kidney disease (CKD), as derived from GWAS, are lacking in the non-African ancestry CKD population; thus, in this perspective, we provide examples of and considerations for using positive controls among patients with CKD. Using data from individuals with CKD who participated in the CRIC (Chronic Renal Insufficiency Cohort) Study or PediGFR (Pediatric Investigation for Genetic Factors Linked to Renal Progression) Consortium, we evaluated 2 kinds of positive control traits: traits unrelated to kidney function (bilirubin level and body height) and those related to kidney function (cystatin C and urate levels). For the former, the proportion of variance in the control trait that is explained by the control SNP is the main determinant of the strength of the observable association, irrespective of adjustment for kidney function. For the latter, adjustment for kidney function can be effective in uncovering known associations among patients with CKD. For instance, in 1,092 participants in the PediGFR Consortium, the P value for the association of cystatin C concentrations and rs911119 in the CST3 gene decreased from 2.7×10(-3) to 2.4×10(-8) upon adjustment for serum creatinine-based estimated glomerular filtration rate. In this perspective, we give recommendations for the appropriate selection of control traits and SNPs that can be used for data checks prior to conducting GWAS among patients with CKD.

  2. Genome-Wide Association Study on Resistance to Stalk Rot Diseases in Grain Sorghum.

    Science.gov (United States)

    Adeyanju, Adedayo; Little, Christopher; Yu, Jianming; Tesso, Tesfaye

    2015-04-16

    Stalk rots are important biotic constraints to sorghum production worldwide. Several pathogens may be associated with the disease, but Macrophomina phaseolina and Fusarium thapsinum are recognized as the major causal organisms. The diseases become more aggressive when drought and high-temperature stress occur during grain filling. Progress in genetic improvement efforts has been slow due to lack of effective phenotyping protocol and the strong environmental effect on disease incidence and severity. Deployment of modern molecular tools is expected to accelerate efforts to develop resistant hybrids. This study was aimed at identifying genomic regions associated with resistance to both causal organisms. A sorghum diversity panel consisting of 300 genotypes assembled from different parts of the world was evaluated for response to infection by both pathogens. Community resources of 79,132 single nucleotide polymorphic (SNP) markers developed on the panel were used in association studies using a multi-locus mixed model to map loci associated with stalk rot resistance. Adequate genetic variation was observed for resistance to both pathogens. Structure analysis grouped the genotypes into five subpopulations primarily based on the racial category of the genotypes. Fourteen loci and a set of candidate genes appear to be involved in connected functions controlling plant defense response. However, each associated SNP had relatively small effect on the traits, accounting for 19-30% of phenotypic variation. Linkage disequilibrium analyses suggest that significant SNPs are genetically independent. Estimation of frequencies of associated alleles revealed that durra and caudatum subpopulations were enriched for resistant alleles, but the results suggest complex molecular mechanisms underlying resistance to both pathogens. Copyright © 2015 Adeyanju et al.

  3. Progress in studies of sex determination mechanisms and sex control techniques in Cynoglossus semilaevis (half-smooth tongue sole

    Directory of Open Access Journals (Sweden)

    Qian ZHOU,Songlin CHEN

    2016-06-01

    Full Text Available The Cynoglossus semilaevis (half-smooth tongue sole is a marine flatfish of great commercial value for fisheries and aquaculture in China. It has a female heterogametic sex determination system (ZW/ZZ and environmental factors can induce sex-reversal of females to phenotypic males, suggesting that it is a promising model for the study of sex determination mechanisms. Additionally, females grow much faster than males and it is feasible to improve the aquaculture production through sex control techniques. This paper reviews the progress in research on sex determination mechanisms research in our laboratory. We have completed whole-genome sequencing and revealed the genome organization and sex chromosome evolution of C. semilaevis. A putative male determining gene dmrt1 was identified and DNA methylation was verified as having a crucial role in the sex reversal process. Genetic maps and sex-specific biomarkers have been used in a marker-assisted selection breeding program and for differentiation of the fish sex. Development and improvement of sex control technologies, including artificial gynogenesis and production of breeding fry with high proportion of females, is also reviewed. These research advances have provided insight into the regulation of sex determination and enabled efficient sex management in artificial culturing of C. semilaevis.

  4. Mapping the sensory perception of apple using descriptive sensory evaluation in a genome wide association study.

    Science.gov (United States)

    Amyotte, Beatrice; Bowen, Amy J; Banks, Travis; Rajcan, Istvan; Somers, Daryl J

    2017-01-01

    Breeding apples is a long-term endeavour and it is imperative that new cultivars are selected to have outstanding consumer appeal. This study has taken the approach of merging sensory science with genome wide association analyses in order to map the human perception of apple flavour and texture onto the apple genome. The goal was to identify genomic associations that could be used in breeding apples for improved fruit quality. A collection of 85 apple cultivars was examined over two years through descriptive sensory evaluation by a trained sensory panel. The trained sensory panel scored randomized sliced samples of each apple cultivar for seventeen taste, flavour and texture attributes using controlled sensory evaluation practices. In addition, the apple collection was subjected to genotyping by sequencing for marker discovery. A genome wide association analysis suggested significant genomic associations for several sensory traits including juiciness, crispness, mealiness and fresh green apple flavour. The findings include previously unreported genomic regions that could be used in apple breeding and suggest that similar sensory association mapping methods could be applied in other plants.

  5. A study on the late core melt progression in pressurized water reactor severe accidents

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jae Hong; Jeun Gyoo Dong; Bang, Kwang Hyun; Park, Seh In; Lim, Jae Hyuck; Park, Seong Yong [Hanyang Univ., Seoul (Korea, Republic of); Back, Hyung Hmm [Korea Maritime Univ., Busan (Korea, Republic of)

    1998-03-15

    After TMI-2 accidents, it has been paid much attention to severe accidents beyond the design basis accidents and the research on the progress of severe accidents and mitigation and the closure of severe accidents has been actively performed. In particular, a great deal of uncertainties yet exist in the phase of late core melt progression and thus the research on this phase of severe accident progress has a key role in obtaining in severe accident mitigation and nuclear reactor safety. In the present study, physics of late core melt progression, experimental data and the major phenomenological models of computer codes are reviewed and a direction of reducing the uncertainties in the late core melt progression os proposed.

  6. Genomics of Sorghum

    OpenAIRE

    PATERSON, ANDREW H

    2008-01-01

    Sorghum (Sorghum bicolor (L.) Moench) is a subject of plant genomics research based on its importance as one of the world's leading cereal crops, a biofuels crop of high and growing importance, a progenitor of one of the world's most noxious weeds, and a botanical model for many tropical grasses with complex genomes. A rich history of genome analysis, culminating in the recent complete sequencing of the genome of a leading inbred, provides a foundation for invigorating progress toward relatin...

  7. Genome wide association studies for body conformation traits in the Chinese Holstein cattle population

    DEFF Research Database (Denmark)

    Wu, Xiaoping; Fang, Ming; Liu, Lin;

    2013-01-01

    Background: Genome-wide association study (GWAS) is a powerful tool for revealing the genetic basis of quantitative traits. However, studies using GWAS for conformation traits of cattle is comparatively less. This study aims to use GWAS to find the candidates genes for body conformation traits.......Results: The Illumina BovineSNP50 BeadChip was used to identify single nucleotide polymorphisms (SNPs) that are associated with body conformation traits. A least absolute shrinkage and selection operator (LASSO) was applied to detect multiple SNPs simultaneously for 29 body conformation traits with 1,314 Chinese...... Holstein cattle and 52,166 SNPs. Totally, 59 genome-wide significant SNPs associated with 26 conformation traits were detected by genome-wide association analysis; five SNPs were within previously reported QTL regions (Animal Quantitative Trait Loci (QTL) database) and 11 were very close to the reported...

  8. [Study on an inquiry-based teaching case in genomics curriculum: identifying virulence factors of Escherichia coli by using comparative genomics].

    Science.gov (United States)

    Jidong, Zhou; Yudong, Li

    2015-02-01

    Genomics is the core subject of various "omics" and it also becomes a topic of increasing interest in undergraduate curricula of biological sciences. However, the study on teaching methodology of genomics courses was very limited so far. Here we report an application of inquiry-based teaching in genomics courses by using virulence factors of Escherichia coli as an example of comparative genomics study. Specially, students first built a multiple-genome alignment of different E. coli strains to investigate the gene conservation using the Mauve tool; then putative virulence factor genes were identified by using BLAST tool to obtain gene annotations. The teaching process was divided into five modules: situation, resources, task, process and evaluation. Learning-assessment results revealed that students had acquired the knowledge and skills of genomics, and their learning interest and ability of self-study were also motivated. Moreover, the special teaching case can be applied to other related courses, such as microbiology, bioinformatics, molecular biology and food safety detection technology.

  9. Using Nematostella vectensis to study the interactions between genome, epigenome and bacteria in a changing environment

    Directory of Open Access Journals (Sweden)

    Sebastian Fraune

    2016-08-01

    Full Text Available The phenotype of an animal cannot be explained entirely by its genes. It is now clear that factors other than the genome contribute to the ecology and evolution of animals. Two fundamentally important factors are the associated microbiota and epigenetic regulations. Unlike the genes and regulatory regions of the genome, epigenetics and microbial composition can be rapidly modified, and may thus represent mechanisms for rapid acclimation to a changing environment. At present, the individual functions of epigenetics, microbiomes, and genomic mutations are largely studied in isolation, particularly for species in marine ecosystems. This single variable approach leaves significant questions open for how these mechanisms intersect in the acclimation and adaptation of organisms in different environments. Here, we propose that the starlet sea anemone, Nematostella vectensis, is a model of choice to investigate the complex interplay between adaptation as well as physiological and molecular plasticity in coastal ecosystems. N. vectensis’ geographic range spans four distinct coastlines, including a wide thermocline along the Atlantic coast of North America. N. vectensis is a particularly powerful invertebrate model for studying genome-environment interactions due to (1 the availability of a well-annotated genome, including preexisting data on genome methylation, histone modifications and miRNAs, (2 an extensive molecular toolkit including well-developed protocols for gene suppression and transgenesis, and (3 the simplicity of culture and experimentation in the laboratory. Taken together, N. vectensis has the tractability to connect the functional relationships between a host animal, microbes, and genome modifications to determine mechanisms underlying phenotypic plasticity and local adaptation.

  10. Drosophila and genome-wide association studies: a review and resource for the functional dissection of human complex traits

    Science.gov (United States)

    Wangler, Michael F.; Hu, Yanhui

    2017-01-01

    ABSTRACT Human genome-wide association studies (GWAS) have successfully identified thousands of susceptibility loci for common diseases with complex genetic etiologies. Although the susceptibility variants identified by GWAS usually have only modest effects on individual disease risk, they contribute to a substantial burden of trait variation in the overall population. GWAS also offer valuable clues to disease mechanisms that have long proven to be elusive. These insights could lead the way to breakthrough treatments; however, several challenges hinder progress, making innovative approaches to accelerate the follow-up of results from GWAS an urgent priority. Here, we discuss the largely untapped potential of the fruit fly, Drosophila melanogaster, for functional investigation of findings from human GWAS. We highlight selected examples where strong genomic conservation with humans along with the rapid and powerful genetic tools available for flies have already facilitated fine mapping of association signals, elucidated gene mechanisms, and revealed novel disease-relevant biology. We emphasize current research opportunities in this rapidly advancing field, and present bioinformatic analyses that systematically explore the applicability of Drosophila for interrogation of susceptibility signals implicated in more than 1000 human traits, based on all GWAS completed to date. Thus, our discussion is targeted at both human geneticists seeking innovative strategies for experimental validation of findings from GWAS, as well as the Drosophila research community, by whom ongoing investigations of the implicated genes will powerfully inform our understanding of human disease. PMID:28151408

  11. Bio-informatics Research Progress in the Post-genome Era Based on the Quantitative Analysis of SCIE

    Institute of Scientific and Technical Information of China (English)

    Yongqin; ZHAN; Min; YU

    2013-01-01

    SCIE paper output can reflect the status quo and trend of discipline research and 7 038 scientific articles concerning bioinformatics are retrieved in SCIE database during the years between 2008 and 2012. Quantitative analysis of paper output and citation frequency are conducted according to nations, institutions, publications, research direction as well as hot articles, which provides assistance for bioinformatics researchers to understand the present situation of this subject, carry out cooperative studies and display scientific research achievements.

  12. Reporting of Human Genome Epidemiology (HuGE association studies: An empirical assessment

    Directory of Open Access Journals (Sweden)

    Gwinn Marta

    2008-05-01

    Full Text Available Abstract Background Several thousand human genome epidemiology association studies are published every year investigating the relationship between common genetic variants and diverse phenotypes. Transparent reporting of study methods and results allows readers to better assess the validity of study findings. Here, we document reporting practices of human genome epidemiology studies. Methods Articles were randomly selected from a continuously updated database of human genome epidemiology association studies to be representative of genetic epidemiology literature. The main analysis evaluated 315 articles published in 2001–2003. For a comparative update, we evaluated 28 more recent articles published in 2006, focusing on issues that were poorly reported in 2001–2003. Results During both time periods, most studies comprised relatively small study populations and examined one or more genetic variants within a single gene. Articles were inconsistent in reporting the data needed to assess selection bias and the methods used to minimize misclassification (of the genotype, outcome, and environmental exposure or to identify population stratification. Statistical power, the use of unrelated study participants, and the use of replicate samples were reported more often in articles published during 2006 when compared with the earlier sample. Conclusion We conclude that many items needed to assess error and bias in human genome epidemiology association studies are not consistently reported. Although some improvements were seen over time, reporting guidelines and online supplemental material may help enhance the transparency of this literature.

  13. Genome-wide association study of generalized anxiety symptoms in the Hispanic Community Health Study/Study of Latinos.

    Science.gov (United States)

    Dunn, Erin C; Sofer, Tamar; Gallo, Linda C; Gogarten, Stephanie M; Kerr, Kathleen F; Chen, Chia-Yen; Stein, Murray B; Ursano, Robert J; Guo, Xiuqing; Jia, Yucheng; Qi, Qibin; Rotter, Jerome I; Argos, Maria; Cai, Jianwen; Penedo, Frank J; Perreira, Krista; Wassertheil-Smoller, Sylvia; Smoller, Jordan W

    2017-03-01

    Although generalized anxiety disorder (GAD) is heritable and aggregates in families, no genomic loci associated with GAD have been reported. We aimed to discover potential loci by conducting a genome-wide analysis of GAD symptoms in a large, population-based sample of Hispanic/Latino adults. Data came from 12,282 participants (aged 18-74) in the Hispanic Community Health Study/Study of Latinos. Using a shortened Spielberger Trait Anxiety measure, we analyzed the following: (i) a GAD symptoms score restricted to the three items tapping diagnostic features of GAD as defined by DSM-V; and (ii) a total trait anxiety score based on summing responses to all ten items. We first calculated the heritability due to common variants (h(2)SNP ) and then conducted a genome-wide association study (GWAS) of GAD symptoms. Replication was attempted in three independent Hispanic cohorts (Multi-Ethnic Study of Atherosclerosis, Women's Health Initiative, Army STARRS). The GAD symptoms score showed evidence of modest heritability (7.2%; P = 0.03), while the total trait anxiety score did not (4.97%; P = 0.20). One genotyped SNP (rs78602344) intronic to thrombospondin 2 (THBS2) was nominally associated (P = 5.28 × 10(-8) ) in the primary analysis adjusting for psychiatric medication use and significantly associated with the GAD symptoms score in the analysis excluding medication users (P = 4.18 × 10(-8) ). However, meta-analysis of the replication samples did not support this association. Although we identified a genome-wide significant locus in this sample, we were unable to replicate this finding. Evidence for heritability was also only detected for GAD symptoms, and not the trait anxiety measure, suggesting differential genetic influences within the domain of trait anxiety. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Tijuana River National Wildlife Refuge contaminant study: Progress report

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — A contaminant study was initiated at Tijuana Slough National Wildlife Refuge in 1987, as a result of concern for pollution from a variety of potential sources. To...

  15. Bowdoin National Wildlife Refuge contaminant biomonitoring study: Progress report

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The purpose of this study was to determine the extent of trace element contamination, particularly boron and selenium, and organochlorine contamination in sediment...

  16. Comparative Genomic Study of the Thioredoxin Family in Photosynthetic Organisms with Emphasis on Populus trichocarpa

    Institute of Scientific and Technical Information of China (English)

    Kamel Chibani; Gunnar Wingsle; Jean-Pierre Jacquot; Eric Gelhaye; Nicolas Rouhier

    2009-01-01

    The recent genome sequencing of Populus trichocarpa and Vitis vinifera, two models of woody plants, of Sorghum bicolor, a model of monocot using C4 metabolism, and of the moss Physcomitrella patens, together with the availability of photosynthetic organism genomes allows performance of a comparative genomic study with organisms having different ways of life, reproduction modes, biological traits, and physiologies. Thioredoxins (Trxs) are small ubiq-uitous proteins involved in the reduction of disulfide bridges in a variety of target enzymes present in all sub-cellular compartments and involved in many biochemical reactions. The genes coding for these enzymes have been identified in these newly sequenced genomes and annotated. The gene content, organization and distribution were compared to other photosynthetic organisms, leading to a refined classification. This analysis revealed that higher plants and bryo-phytes have a more complex family compared to algae and cyanobacteria and to non-photosynthetic organisms, since poplar exhibits 49 genes coding for typical and atypical thioredoxins and thioredoxin reductases, namely one-third more than monocots such as Oryza sativa and S. bicolor. The higher number of Trxs in poplar is partially explained by gene duplication in the Trx m, h, and nucleoredoxin classes. Particular attention was paid to poplar genes with emphasis on Trx-like classes called Clot, thioredoxin-like, thioredoxins of the lilium type and nucleoredoxins, which were not described in depth in previous genomic studies.

  17. Studies on the genomic association between schistosomiasis and hepatitis C virus infection

    Directory of Open Access Journals (Sweden)

    Akram M Abou-Zied

    2015-01-01

    Full Text Available Background: Schistosomiasis is an infection caused by blood flukes of the genus Schistosoma. Schistosomes are successful parasites, apparently as a result of prolonged co-evolution with their hosts. Studies done nationwide in Egypt found the highest risk of hepatitis C virus (HCV co-infection is in those infested with schistosome without history of blood transfusions. However, the association between schistosomiasis and HCV infection is incompletely understood. Aims: The overall aim of this study was to assess whether or not a genomic association between schistosomal infestation and HCV infection exists. Materials and Methods: Oligonucleotide specific primers of HCV-polymerase chain reaction (PCR diagnostics were used to screen the genomic DNA and cDNA library pool of Schistosoma mansoni as templates based on the end-point PCR approach. Results: Screening of schistosome DNA by PCR, lead to the detection of sequences similar to HCV. PCR products were obtained when adult worms genomic DNA were used as templates while no PCR products were amplified from S. mansoni λZAPII cDNA library pool. The resulting PCR products were sequenced and compared with the other closely related HCV sequence database at the website . Conclusions: This work demonstrates the existence of HCV and its replication in the genomic DNA of S. mansoni. In addition, it highlights the fact that the parasite can carry the virus genome and therefore, is considered as a nonhuman vector for the transmission of HCV infections.

  18. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

    NARCIS (Netherlands)

    Wain, Louise V.; Verwoert, Germaine C.; O'Reilly, Paul F.; Shi, Gang; Johnson, Toby; Johnson, Andrew D.; Bochud, Murielle; Rice, Kenneth M.; Henneman, Peter; Smith, Albert V.; Ehret, Georg B.; Amin, Najaf; Larson, Martin G.; Mooser, Vincent; Hadley, David; Doerr, Marcus; Bis, Joshua C.; Aspelund, Thor; Esko, Tonu; Janssens, A. Cecile J. W.; Zhao, Jing Hua; Heath, Simon; Laan, Maris; Fu, Jingyuan; Pistis, Giorgio; Luan, Jian'an; Arora, Pankaj; Lucas, Gavin; Pirastu, Nicola; Pichler, Irene; Jackson, Anne U.; Webster, Rebecca J.; Zhang, Feng; Peden, John F.; Schmidt, Helena; Tanaka, Toshiko; Campbell, Harry; Igl, Wilmar; Milaneschi, Yuri; Hottenga, Jouke-Jan; Vitart, Veronique; Chasman, Daniel I.; Trompet, Stella; Bragg-Gresham, Jennifer L.; Alizadeh, Behrooz Z.; Chambers, John C.; Guo, Xiuqing; Lehtimaki, Terho; Kuehnel, Brigitte; Lopez, Lorna M.; Polasek, Ozren; Boban, Mladen; Nelson, Christopher P.; Morrison, Alanna C.; Pihur, Vasyl; Ganesh, Santhi K.; Hofman, Albert; Kundu, Suman; Mattace-Raso, Francesco U. S.; Rivadeneira, Fernando; Sijbrands, Eric J. G.; Uitterlinden, Andre G.; Hwang, Shih-Jen; Vasan, Ramachandran S.; Wang, Thomas J.; Bergmann, Sven; Vollenweider, Peter; Waeber, Gerard; Laitinen, Jaana; Pouta, Anneli; Zitting, Paavo; McArdle, Wendy L.; Kroemer, Heyo K.; Voelker, Uwe; Voelzke, Henry; Glazer, Nicole L.; Taylor, Kent D.; Harris, Tamara B.; Alavere, Helene; Haller, Toomas; Keis, Aime; Tammesoo, Mari-Liis; Aulchenko, Yurii; Barroso, Ines; Khaw, Kay-Tee; Galan, Pilar; Hercberg, Serge; Lathrop, Mark; Eyheramendy, Susana; Org, Elin; Sober, Siim; Lu, Xiaowen; Nolte, Ilja M.; Penninx, Brenda W.; Corre, Tanguy; Masciullo, Corrado; Sala, Cinzia; Groop, Leif; Voight, Benjamin F.; Melander, Olle; O'Donnell, Christopher J.; Salomaa, Veikko; d'Adamo, Adamo Pio; Fabretto, Antonella; Faletra, Flavio; Ulivi, Sheila; Del Greco, Fabiola M.; Facheris, Maurizio; Collins, Francis S.; Bergman, Richard N.; Beilby, John P.; Hung, Joseph; Musk, A. William; Mangino, Massimo; Shin, So-Youn; Soranzo, Nicole; Watkins, Hugh; Goel, Anuj; Hamsten, Anders; Gider, Pierre; Loitfelder, Marisa; Zeginigg, Marion; Hernandez, Dena; Najjar, Samer S.; Navarro, Pau; Wild, Sarah H.; Corsi, Anna Maria; Singleton, Andrew; de Geus, Eco J. C.; Willemsen, Gonneke; Parker, Alex N.; Rose, Lynda M.; Buckley, Brendan; Stott, David; Orru, Marco; Uda, Manuela; van der Klauw, Melanie M.; Zhang, Weihua; Li, Xinzhong; Scott, James; Chen, Yii-Der Ida; Burke, Gregory L.; Kahonen, Mika; Viikari, Jorma; Doering, Angela; Meitinger, Thomas; Davies, Gail; Starr, John M.; Emilsson, Valur; Plump, Andrew; Lindeman, Jan H.; 't Hoen, Peter A. C.; Koenig, Inke R.; Felix, Janine F.; Clarke, Robert; Hopewell, Jemma C.; Ongen, Halit; Breteler, Monique; Debette, Stephanie; DeStefano, Anita L.; Fornage, Myriam; Mitchell, Gary F.; Smith, Nicholas L.; Holm, Hilma; Stefansson, Kari; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Samani, Nilesh J.; Preuss, Michael; Rudan, Igor; Hayward, Caroline; Deary, Ian J.; Wichmann, H-Erich; Raitakari, Olli T.; Palmas, Walter; Kooner, Jaspal S.; Stolk, Ronald P.; Jukema, J. Wouter; Wright, Alan F.; Boomsma, Dorret I.; Bandinelli, Stefania; Gyllensten, Ulf B.; Wilson, James F.; Ferrucci, Luigi; Schmidt, Reinhold; Farrall, Martin; Spector, Tim D.; Palmer, Lyle J.; Tuomilehto, Jaakko; Pfeufer, Arne; Gasparini, Paolo; Siscovick, David; Altshuler, David; Loos, Ruth J. F.; Toniolo, Daniela; Snieder, Harold; Gieger, Christian; Meneton, Pierre; Wareham, Nicholas J.; Oostra, Ben A.; Metspalu, Andres; Launer, Lenore; Rettig, Rainer; Strachan, David P.; Beckmann, Jacques S.; Witteman, Jacqueline C. M.; Erdmann, Jeanette; van Dijk, Ko Willems; Boerwinkle, Eric; Boehnke, Michael; Ridker, Paul M.; Jarvelin, Marjo-Riitta; Chakravarti, Aravinda; Abecasis, Goncalo R.; Gudnason, Vilmundur; Newton-Cheh, Christopher; Levy, Daniel; Munroe, Patricia B.; Psaty, Bruce M.; Caulfield, Mark J.; Rao, Dabeeru C.; Tobin, Martin D.; Elliott, Paul; van Duijn, Cornelia M.

    2011-01-01

    Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans(1-3). We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we

  19. Genome-wide association study identifies multiple susceptibility loci for multiple myeloma

    DEFF Research Database (Denmark)

    Mitchell, Jonathan S; Li, Ni; Weinhold, Niels;

    2016-01-01

    Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a ...

  20. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

    NARCIS (Netherlands)

    L.V. Wain (Louise); G.C. Verwoert (Germaine); P.F. O'Reilly (Paul); G. Shi (Gang); T. Johnson (Toby); M. Bochud (Murielle); K. Rice (Kenneth); P. Henneman (Peter); A.V. Smith (Albert Vernon); G.B. Ehret (Georg); N. Amin (Najaf); M.G. Larson (Martin); V. Mooser (Vincent); D. Hadley (David); M. Dörr (Marcus); J.C. Bis (Joshua); T. Aspelund (Thor); T. Esko (Tõnu); A.C.J.W. Janssens (Cécile); J.H. Zhao; S.C. Heath (Simon); M. Laan (Maris); J. Fu (Jingyuan); G. Pistis (Giorgio); J. Luan; G. Lucas (Gavin); N. Pirastu (Nicola); I. Pichler (Irene); A.U. Jackson (Anne); R.J. Webster (Rebecca J.); F.F. Zhang; J. Peden (John); R. Schmidt (Reinhold); T. Tanaka (Toshiko); H. Campbell (Harry); W. Igl (Wilmar); Y. Milaneschi (Yuri); J.J. Hottenga (Jouke Jan); V. Vitart (Veronique); D.I. Chasman (Daniel); S. Trompet (Stella); J.L. Bragg-Gresham (Jennifer L.); B.Z. Alizadeh (Behrooz); J.C. Chambers (John); X. Guo (Xiuqing); T. Lehtimäki (Terho); B. Kuhnel (Brigitte); L.M. Lopez; O. Polasek (Ozren); M. Boban (Mladen); C.P. Nelson (Christopher P.); A.C. Morrison (Alanna); V. Pihur (Vasyl); S.K. Ganesh (Santhi); A. Hofman (Albert); S. Kundu (Suman); F.U.S. Mattace Raso (Francesco); F. Rivadeneira Ramirez (Fernando); E.J.G. Sijbrands (Eric); A.G. Uitterlinden (André); S.J. Hwang; R.S. Vasan (Ramachandran Srini); Y.A. Wang (Ying); S.M. Bergmann (Sven); P. Vollenweider (Peter); G. Waeber (Gérard); J. Laitinen (Jaana); A. Pouta (Anneli); P. Zitting (Paavo); W.L. McArdle (Wendy); H.K. Kroemer (Heyo); U. Völker (Uwe); H. Völzke (Henry); N.L. Glazer (Nicole); K.D. Taylor (Kent); T.B. Harris (Tamara); H. Alavere (Helene); T. Haller (Toomas); A. Keis (Aime); M.L. Tammesoo; Y.S. Aulchenko (Yurii); K-T. Khaw (Kay-Tee); P. Galan (Pilar); S. Hercberg (Serge); G.M. Lathrop (Mark); S. Eyheramendy (Susana); E. Org (Elin); S. Sõber (Siim); X. Lu (Xiaowen); I.M. Nolte (Ilja); B.W.J.H. Penninx (Brenda); T. Corre (Tanguy); C. Masciullo (Corrado); C. Sala (Cinzia); L. Groop (Leif); B.F. Voight (Benjamin); O. Melander (Olle); C.J. O'Donnell (Christopher); V. Salomaa (Veikko); P. d' Adamo (Pio); A. Fabretto (Antonella); F. Faletra (Flavio); S. Ulivi (Shelia); F. Del Greco M (Fabiola); M.F. Facheris (Maurizio); F.S. Collins (Francis); R.N. Bergman (Richard); J.P. Beilby (John); J. Hung (Judy); A.W. Musk (Arthur); M. Mangino (Massimo); S.Y. Shin (So Youn); N. Soranzo (Nicole); H. Watkins (Hugh); A. Goel (Anuj); A. Hamsten (Anders); P. Gider (Pierre); M. Loitfelder (Marisa); M. Zeginigg (Marion); D.G. Hernandez (Dena); S.S. Najjar (Samer); P. Navarro (Pau); S.H. Wild (Sarah); A.M. Corsi (Anna Maria); A. Singleton (Andrew); E.J.C. de Geus (Eco); G.A.H.M. Willemsen (Gonneke); A.N. Parker (Alex); L.M. Rose (Lynda); B.M. Buckley (Brendan M.); D.J. Stott (David. J.); M. Orrù (Marco); M. Uda (Manuela); M.M. van der Klauw (Melanie); X. Li (Xiaohui); J. Scott (James); Y.D.I. Chen (Yii-Der Ida); G.L. Burke (Greg); M. Kähönen (Mika); J. Viikari (Jorma); A. Döring (Angela); T. Meitinger (Thomas); G.S. Davis; J.M. Starr (John); V. Emilsson (Valur); A.S. Plump (Andrew); J.H. Lindeman (Jan H.); P.A.C. 't Hoen (Peter); I.R. König (Inke); J.F. Felix (Janine); R. Clarke; J. Hopewell; H. Ongen (Halit); M.M.B. Breteler (Monique); S. Debette (Stéphanie); A.L. DeStefano (Anita); M. Fornage (Myriam); G.F. Mitchell (Gary); H. Holm (Hilma); K. Stefansson (Kari); G. Thorleifsson (Gudmar); U. Thorsteinsdottir (Unnur); N.J. Samani (Nilesh); M. Preuss (Michael); I. Rudan (Igor); C. Hayward (Caroline); I.J. Deary (Ian); H.E. Wichmann (Heinz Erich); O. Raitakari (Olli); W. Palmas (Walter); J.S. Kooner (Jaspal); R.P. Stolk (Ronald); J.W. Jukema (Jan Wouter); A.F. Wright (Alan); D.I. Boomsma (Dorret); S. Bandinelli (Stefania); U. Gyllensten (Ulf); J.F. Wilson (James); L. Ferrucci (Luigi); M. Farrall (Martin); T.D. Spector (Timothy); L.J. Palmer; J. Tuomilehto (Jaakko); A. Pfeufer (Arne); P. Gasparini (Paolo); D.S. Siscovick (David); D. Altshuler (David); R.J.F. Loos (Ruth); D. Toniolo (Daniela); H. Snieder (Harold); C. Gieger (Christian); P. Meneton (Pierre); N.J. Wareham (Nick); B.A. Oostra (Ben); A. Metspalu (Andres); L.J. Launer (Lenore); R. Rettig (Rainer); D.P. Strachan (David); J.S. Beckmann (Jacques); J.C.M. Witteman (Jacqueline); J.A.P. Willems van Dijk (Ko); E.A. Boerwinkle (Eric); M. Boehnke (Michael); P.M. Ridker (Paul); M.R. Järvelin; A. Chakravarti (Aravinda); J. Erdmann (Jeanette); V. Gudnason (Vilmundur); C. Newton-Cheh (Christopher); D. Levy (Daniel); P. Arora (Pankaj)

    2011-01-01

    textabstractNumerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N =

  1. Genome-wide association studies for Agronomical Traits in a world wide Spring Barley Collection

    NARCIS (Netherlands)

    Pasam, R.K.; Sharma, R.; Malosetti, M.; Eeuwijk, van F.A.; Haseneyer, G.; Kilian, B.; Graner, A.

    2012-01-01

    Background Genome-wide association studies (GWAS) based on linkage disequilibrium (LD) provide a promising tool for the detection and fine mapping of quantitative trait loci (QTL) underlying complex agronomic traits. In this study we explored the genetic basis of variation for the traits heading dat

  2. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

    NARCIS (Netherlands)

    Wain, Louise V; Verwoert, Germaine C; O'Reilly, Paul F; Shi, Gang; Johnson, Toby; Johnson, Andrew D; Bochud, Murielle; Rice, Kenneth M; Henneman, Peter; Smith, Albert V; Ehret, Georg B; Amin, Najaf; Larson, Martin G; Mooser, Vincent; Hadley, David; Dörr, Marcus; Bis, Joshua C; Aspelund, Thor; Esko, Tõnu; Janssens, A Cecile J W; Zhao, Jing Hua; Heath, Simon; Laan, Maris; Fu, Jingyuan; Pistis, Giorgio; Luan, Jian'an; Arora, Pankaj; Lucas, Gavin; Pirastu, Nicola; Pichler, Irene; Jackson, Anne U; Webster, Rebecca J; Zhang, Feng; Peden, John F; Schmidt, Helena; Tanaka, Toshiko; Campbell, Harry; Igl, Wilmar; Milaneschi, Yuri; Hottenga, Jouke-Jan; Vitart, Veronique; Chasman, Daniel I; Trompet, Stella; Bragg-Gresham, Jennifer L; Alizadeh, Behrooz Z; Chambers, John C; Guo, Xiuqing; Lehtimäki, Terho; Kühnel, Brigitte; Lopez, Lorna M; Polašek, Ozren; Boban, Mladen; Nelson, Christopher P; Morrison, Alanna C; Pihur, Vasyl; Ganesh, Santhi K; Hofman, Albert; Kundu, Suman; Mattace-Raso, Francesco U S; Rivadeneira, Fernando; Sijbrands, Eric J G; Uitterlinden, Andre G; Hwang, Shih-Jen; Vasan, Ramachandran S; Wang, Thomas J; Bergmann, Sven; Vollenweider, Peter; Waeber, Gérard; Laitinen, Jaana; Pouta, Anneli; Zitting, Paavo; McArdle, Wendy L; Kroemer, Heyo K; Völker, Uwe; Völzke, Henry; Glazer, Nicole L; Taylor, Kent D; Harris, Tamara B; Alavere, Helene; Haller, Toomas; Keis, Aime; Tammesoo, Mari-Liis; Aulchenko, Yurii; Barroso, Inês; Khaw, Kay-Tee; Galan, Pilar; Hercberg, Serge; Lathrop, Mark; Eyheramendy, Susana; Org, Elin; Sõber, Siim; Lu, Xiaowen; Nolte, Ilja M; Penninx, Brenda W; Corre, Tanguy; Masciullo, Corrado; Sala, Cinzia; Groop, Leif; Voight, Benjamin F; Melander, Olle; O'Donnell, Christopher J; Salomaa, Veikko; d'Adamo, Adamo Pio; Fabretto, Antonella; Faletra, Flavio; Ulivi, Sheila; Del Greco, Fabiola M; Facheris, Maurizio; Collins, Francis S; Bergman, Richard N; Beilby, John P; Hung, Joseph; Musk, A William; Mangino, Massimo; Shin, So-Youn; Soranzo, Nicole; Watkins, Hugh; Goel, Anuj; Hamsten, Anders; Gider, Pierre; Loitfelder, Marisa; Zeginigg, Marion; Hernandez, Dena; Najjar, Samer S; Navarro, Pau; Wild, Sarah H; Corsi, Anna Maria; Singleton, Andrew; de Geus, Eco J C; Willemsen, Gonneke; Parker, Alex N; Rose, Lynda M; Buckley, Brendan; Stott, David; Orru, Marco; Uda, Manuela; van der Klauw, Melanie M; Zhang, Weihua; Li, Xinzhong; Scott, James; Chen, Yii-Der Ida; Burke, Gregory L; Kähönen, Mika; Viikari, Jorma; Döring, Angela; Meitinger, Thomas; Davies, Gail; Starr, John M; Emilsson, Valur; Plump, Andrew; Lindeman, Jan H; Hoen, Peter A C 't; König, Inke R; Felix, Janine F; Clarke, Robert; Hopewell, Jemma C; Ongen, Halit; Breteler, Monique; Debette, Stéphanie; Destefano, Anita L; Fornage, Myriam; Mitchell, Gary F; Smith, Nicholas L; Holm, Hilma; Stefansson, Kari; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Samani, Nilesh J; Preuss, Michael; Rudan, Igor; Hayward, Caroline; Deary, Ian J; Wichmann, H-Erich; Raitakari, Olli T; Palmas, Walter; Kooner, Jaspal S; Stolk, Ronald P; Jukema, J Wouter; Wright, Alan F; Boomsma, Dorret I; Bandinelli, Stefania; Gyllensten, Ulf B; Wilson, James F; Ferrucci, Luigi; Schmidt, Reinhold; Farrall, Martin; Spector, Tim D; Palmer, Lyle J; Tuomilehto, Jaakko; Pfeufer, Arne; Gasparini, Paolo; Siscovick, David; Altshuler, David; Loos, Ruth J F; Toniolo, Daniela; Snieder, Harold; Gieger, Christian; Meneton, Pierre; Wareham, Nicholas J; Oostra, Ben A; Metspalu, Andres; Launer, Lenore; Rettig, Rainer; Strachan, David P; Beckmann, Jacques S; Witteman, Jacqueline C M; Erdmann, Jeanette; van Dijk, Ko Willems; Boerwinkle, Eric; Boehnke, Michael; Ridker, Paul M; Jarvelin, Marjo-Riitta; Chakravarti, Aravinda; Abecasis, Goncalo R; Gudnason, Vilmundur; Newton-Cheh, Christopher; Levy, Daniel; Munroe, Patricia B; Psaty, Bruce M; Caulfield, Mark J; Rao, Dabeeru C; Tobin, Martin D; Elliott, Paul; van Duijn, Cornelia M

    2011-01-01

    Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we ident

  3. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

    NARCIS (Netherlands)

    Wain, Louise V.; Verwoert, Germaine C.; O'Reilly, Paul F.; Shi, Gang; Johnson, Toby; Johnson, Andrew D.; Bochud, Murielle; Rice, Kenneth M.; Henneman, Peter; Smith, Albert V.; Ehret, Georg B.; Amin, Najaf; Larson, Martin G.; Mooser, Vincent; Hadley, David; Doerr, Marcus; Bis, Joshua C.; Aspelund, Thor; Esko, Tonu; Janssens, A. Cecile J. W.; Zhao, Jing Hua; Heath, Simon; Laan, Maris; Fu, Jingyuan; Pistis, Giorgio; Luan, Jian'an; Arora, Pankaj; Lucas, Gavin; Pirastu, Nicola; Pichler, Irene; Jackson, Anne U.; Webster, Rebecca J.; Zhang, Feng; Peden, John F.; Schmidt, Helena; Tanaka, Toshiko; Campbell, Harry; Igl, Wilmar; Milaneschi, Yuri; Hottenga, Jouke-Jan; Vitart, Veronique; Chasman, Daniel I.; Trompet, Stella; Bragg-Gresham, Jennifer L.; Alizadeh, Behrooz Z.; Chambers, John C.; Guo, Xiuqing; Lehtimaki, Terho; Kuehnel, Brigitte; Lopez, Lorna M.; Polasek, Ozren; Boban, Mladen; Nelson, Christopher P.; Morrison, Alanna C.; Pihur, Vasyl; Ganesh, Santhi K.; Hofman, Albert; Kundu, Suman; Mattace-Raso, Francesco U. S.; Rivadeneira, Fernando; Sijbrands, Eric J. G.; Uitterlinden, Andre G.; Hwang, Shih-Jen; Vasan, Ramachandran S.; Wang, Thomas J.; Bergmann, Sven; Vollenweider, Peter; Waeber, Gerard; Laitinen, Jaana; Pouta, Anneli; Zitting, Paavo; McArdle, Wendy L.; Kroemer, Heyo K.; Voelker, Uwe; Voelzke, Henry; Glazer, Nicole L.; Taylor, Kent D.; Harris, Tamara B.; Alavere, Helene; Haller, Toomas; Keis, Aime; Tammesoo, Mari-Liis; Aulchenko, Yurii; Barroso, Ines; Khaw, Kay-Tee; Galan, Pilar; Hercberg, Serge; Lathrop, Mark; Eyheramendy, Susana; Org, Elin; Sober, Siim; Lu, Xiaowen; Nolte, Ilja M.; Penninx, Brenda W.; Corre, Tanguy; Masciullo, Corrado; Sala, Cinzia; Groop, Leif; Voight, Benjamin F.; Melander, Olle; O'Donnell, Christopher J.; Salomaa, Veikko; d'Adamo, Adamo Pio; Fabretto, Antonella; Faletra, Flavio; Ulivi, Sheila; Del Greco, Fabiola M.; Facheris, Maurizio; Collins, Francis S.; Bergman, Richard N.; Beilby, John P.; Hung, Joseph; Musk, A. William; Mangino, Massimo; Shin, So-Youn; Soranzo, Nicole; Watkins, Hugh; Goel, Anuj; Hamsten, Anders; Gider, Pierre; Loitfelder, Marisa; Zeginigg, Marion; Hernandez, Dena; Najjar, Samer S.; Navarro, Pau; Wild, Sarah H.; Corsi, Anna Maria; Singleton, Andrew; de Geus, Eco J. C.; Willemsen, Gonneke; Parker, Alex N.; Rose, Lynda M.; Buckley, Brendan; Stott, David; Orru, Marco; Uda, Manuela; van der Klauw, Melanie M.; Zhang, Weihua; Li, Xinzhong; Scott, James; Chen, Yii-Der Ida; Burke, Gregory L.; Kahonen, Mika; Viikari, Jorma; Doering, Angela; Meitinger, Thomas; Davies, Gail; Starr, John M.; Emilsson, Valur; Plump, Andrew; Lindeman, Jan H.; 't Hoen, Peter A. C.; Koenig, Inke R.; Felix, Janine F.; Clarke, Robert; Hopewell, Jemma C.; Ongen, Halit; Breteler, Monique; Debette, Stephanie; DeStefano, Anita L.; Fornage, Myriam; Mitchell, Gary F.; Smith, Nicholas L.; Holm, Hilma; Stefansson, Kari; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Samani, Nilesh J.; Preuss, Michael; Rudan, Igor; Hayward, Caroline; Deary, Ian J.; Wichmann, H-Erich; Raitakari, Olli T.; Palmas, Walter; Kooner, Jaspal S.; Stolk, Ronald P.; Jukema, J. Wouter; Wright, Alan F.; Boomsma, Dorret I.; Bandinelli, Stefania; Gyllensten, Ulf B.; Wilson, James F.; Ferrucci, Luigi; Schmidt, Reinhold; Farrall, Martin; Spector, Tim D.; Palmer, Lyle J.; Tuomilehto, Jaakko; Pfeufer, Arne; Gasparini, Paolo; Siscovick, David; Altshuler, David; Loos, Ruth J. F.; Toniolo, Daniela; Snieder, Harold; Gieger, Christian; Meneton, Pierre; Wareham, Nicholas J.; Oostra, Ben A.; Metspalu, Andres; Launer, Lenore; Rettig, Rainer; Strachan, David P.; Beckmann, Jacques S.; Witteman, Jacqueline C. M.; Erdmann, Jeanette; van Dijk, Ko Willems; Boerwinkle, Eric; Boehnke, Michael; Ridker, Paul M.; Jarvelin, Marjo-Riitta; Chakravarti, Aravinda; Abecasis, Goncalo R.; Gudnason, Vilmundur; Newton-Cheh, Christopher; Levy, Daniel; Munroe, Patricia B.; Psaty, Bruce M.; Caulfield, Mark J.; Rao, Dabeeru C.; Tobin, Martin D.; Elliott, Paul; van Duijn, Cornelia M.

    2011-01-01

    Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans(1-3). We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we

  4. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

    NARCIS (Netherlands)

    L.V. Wain (Louise); G.C. Verwoert (Germaine); P.F. O'Reilly (Paul); G. Shi (Gang); T. Johnson (Toby); M. Bochud (Murielle); K. Rice (Kenneth); P. Henneman (Peter); A.V. Smith (Albert Vernon); G.B. Ehret (Georg); N. Amin (Najaf); M.G. Larson (Martin); V. Mooser (Vincent); D. Hadley (David); M. Dörr (Marcus); J.C. Bis (Joshua); T. Aspelund (Thor); T. Esko (Tõnu); A.C.J.W. Janssens (Cécile); J.H. Zhao; S.C. Heath (Simon); M. Laan (Maris); J. Fu (Jingyuan); G. Pistis (Giorgio); J. Luan; G. Lucas (Gavin); N. Pirastu (Nicola); I. Pichler (Irene); A.U. Jackson (Anne); R.J. Webster (Rebecca J.); F.F. Zhang; J. Peden (John); R. Schmidt (Reinhold); T. Tanaka (Toshiko); H. Campbell (Harry); W. Igl (Wilmar); Y. Milaneschi (Yuri); J.J. Hottenga (Jouke Jan); V. Vitart (Veronique); D.I. Chasman (Daniel); S. Trompet (Stella); J.L. Bragg-Gresham (Jennifer L.); B.Z. Alizadeh (Behrooz); J.C. Chambers (John); X. Guo (Xiuqing); T. Lehtimäki (Terho); B. Kuhnel (Brigitte); L.M. Lopez; O. Polasek (Ozren); M. Boban (Mladen); C.P. Nelson (Christopher P.); A.C. Morrison (Alanna); V. Pihur (Vasyl); S.K. Ganesh (Santhi); A. Hofman (Albert); S. Kundu (Suman); F.U.S. Mattace Raso (Francesco); F. Rivadeneira Ramirez (Fernando); E.J.G. Sijbrands (Eric); A.G. Uitterlinden (André); S.J. Hwang; R.S. Vasan (Ramachandran Srini); Y.A. Wang (Ying); S.M. Bergmann (Sven); P. Vollenweider (Peter); G. Waeber (Gérard); J. Laitinen (Jaana); A. Pouta (Anneli); P. Zitting (Paavo); W.L. McArdle (Wendy); H.K. Kroemer (Heyo); U. Völker (Uwe); H. Völzke (Henry); N.L. Glazer (Nicole); K.D. Taylor (Kent); T.B. Harris (Tamara); H. Alavere (Helene); T. Haller (Toomas); A. Keis (Aime); M.L. Tammesoo; Y.S. Aulchenko (Yurii); K-T. Khaw (Kay-Tee); P. Galan (Pilar); S. Hercberg (Serge); G.M. Lathrop (Mark); S. Eyheramendy (Susana); E. Org (Elin); S. Sõber (Siim); X. Lu (Xiaowen); I.M. Nolte (Ilja); B.W.J.H. Penninx (Brenda); T. Corre (Tanguy); C. Masciullo (Corrado); C. Sala (Cinzia); L. Groop (Leif); B.F. Voight (Benjamin); O. Melander (Olle); C.J. O'Donnell (Christopher); V. Salomaa (Veikko); P. d' Adamo (Pio); A. Fabretto (Antonella); F. Faletra (Flavio); S. Ulivi (Shelia); F. Del Greco M (Fabiola); M.F. Facheris (Maurizio); F.S. Collins (Francis); R.N. Bergman (Richard); J.P. Beilby (John); J. Hung (Judy); A.W. Musk (Arthur); M. Mangino (Massimo); S.Y. Shin (So Youn); N. Soranzo (Nicole); H. Watkins (Hugh); A. Goel (Anuj); A. Hamsten (Anders); P. Gider (Pierre); M. Loitfelder (Marisa); M. Zeginigg (Marion); D.G. Hernandez (Dena); S.S. Najjar (Samer); P. Navarro (Pau); S.H. Wild (Sarah); A.M. Corsi (Anna Maria); A. Singleton (Andrew); E.J.C. de Geus (Eco); G.A.H.M. Willemsen (Gonneke); A.N. Parker (Alex); L.M. Rose (Lynda); B.M. Buckley (Brendan M.); D.J. Stott (David. J.); M. Orrù (Marco); M. Uda (Manuela); M.M. van der Klauw (Melanie); X. Li (Xiaohui); J. Scott (James); Y.D.I. Chen (Yii-Der Ida); G.L. Burke (Greg); M. Kähönen (Mika); J. Viikari (Jorma); A. Döring (Angela); T. Meitinger (Thomas); G.S. Davis; J.M. Starr (John); V. Emilsson (Valur); A.S. Plump (Andrew); J.H. Lindeman (Jan H.); P.A.C. 't Hoen (Peter); I.R. König (Inke); J.F. Felix (Janine); R. Clarke; J. Hopewell; H. Ongen (Halit); M.M.B. Breteler (Monique); S. Debette (Stéphanie); A.L. DeStefano (Anita); M. Fornage (Myriam); G.F. Mitchell (Gary); H. Holm (Hilma); K. Stefansson (Kari); G. Thorleifsson (Gudmar); U. Thorsteinsdottir (Unnur); N.J. Samani (Nilesh); M. Preuss (Michael); I. Rudan (Igor); C. Hayward (Caroline); I.J. Deary (Ian); H.E. Wichmann (Heinz Erich); O. Raitakari (Olli); W. Palmas (Walter); J.S. Kooner (Jaspal); R.P. Stolk (Ronald); J.W. Jukema (Jan Wouter); A.F. Wright (Alan); D.I. Boomsma (Dorret); S. Bandinelli (Stefania); U. Gyllensten (Ulf); J.F. Wilson (James); L. Ferrucci (Luigi); M. Farrall (Martin); T.D. Spector (Timothy); L.J. Palmer; J. Tuomilehto (Jaakko); A. Pfeufer (Arne); P. Gasparini (Paolo); D.S. Siscovick (David); D. Altshuler (David); R.J.F. Loos (Ruth); D. Toniolo (Daniela); H. Snieder (Harold); C. Gieger (Christian); P. Meneton (Pierre); N.J. Wareham (Nick); B.A. Oostra (Ben); A. Metspalu (Andres); L.J. Launer (Lenore); R. Rettig (Rainer); D.P. Strachan (David); J.S. Beckmann (Jacques); J.C.M. Witteman (Jacqueline); J.A.P. Willems van Dijk (Ko); E.A. Boerwinkle (Eric); M. Boehnke (Michael); P.M. Ridker (Paul); M.R. Järvelin; A. Chakravarti (Aravinda); J. Erdmann (Jeanette); V. Gudnason (Vilmundur); C. Newton-Cheh (Christopher); D. Levy (Daniel); P. Arora (Pankaj); P. Munroe (Patricia); B.M. Psaty (Bruce); M. Caulfield (Mark); D.C. Rao (Dabeeru C.); P. Elliott (Paul); P. Tikka-Kleemola (Päivi); G.R. Abecasis (Gonçalo); I. Barroso (Inês)

    2011-01-01

    textabstractNumerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,60

  5. Genomic analysis for managing small and endangered populations: A case study in Tyrol Grey cattle

    Directory of Open Access Journals (Sweden)

    Gábor eMészáros

    2015-05-01

    Full Text Available Analysis of genomic data is increasingly becoming part of the livestock industry. Therefore the routine collection of genomic information would be an invaluable resource for management of breeding programs in small, endangered populations. The objectives of this project were to analyse 1. linkage disequlibrium decay and the effective population size; 2. Inbreeding level and effective population size (NeROH based on runs of homozygosity (ROH; 3. Prediction of genomic breeding values (GEBV within and across breeds. In addition, the use of genomic information for breed management is discussed. The study was based on all available genotypes of Tyrol Grey AI bulls. ROHs were derived based on regions covering at least 4 Mb, 8 Mb and 16 Mb regions, with the corresponding mean inbreeding coefficients 4.0%, 2.9% and 1.6%, respectively. The NeROH was 125 (NeROH>16Mb, 186 (NeROH>8Mb and 370 (NeROH>4Mb, indicating strict avoidance of close inbreeding in the population.The genomic selection was developed for and is working well in large breeds. Contrary to the expectations, the accuracy of GEBVs with very small within breed reference populations were very high, between 0.13-0.91 and 0.12-0.63, when EBVs and dEBVs were used as pseudo-phenotypes, respectively. Subsequent analyses confirmed the high accuracies being heavily influenced by parent averages. Multi-breed and across breed reference sets gave inconsistent and lower accuracies. Genomic information may have a crucial role in management of small breeds. It allows to assess relatedness between individuals, trends in inbreeding and to take decisions accordingly. These decisions would be based on the real genome architecture, rather than conventional pedigree information, which can be missing or incomplete. We strongly suggest the routine genotyping of all individuals that belong to a small breed in order to facilitate the effective management of endangered livestock populations.

  6. Evaluation of Study and Patient Characteristics of Clinical Studies in Primary Progressive Multiple Sclerosis: A Systematic Review.

    Directory of Open Access Journals (Sweden)

    T Ziemssen

    Full Text Available So far, clinical studies in primary progressive MS (PPMS have failed to meet their primary efficacy endpoints. To some extent this might be attributable to the choice of assessments or to the selection of the study population.The aim of this study was to identify outcome influencing factors by analyzing the design and methods of previous randomized studies in PPMS patients without restriction to intervention or comparator.A systematic literature search was conducted in MEDLINE, EMBASE, BIOSIS and the COCHRANE Central Register of Controlled Trials (inception to February 2015. Keywords included PPMS, primary progressive multiple sclerosis and chronic progressive multiple sclerosis. Randomized, controlled trials of at least one year's duration were selected if they included only patients with PPMS or if they reported sufficient PPMS subgroup data. No restrictions with respect to intervention or comparator were applied. Study quality was assessed by a biometrics expert. Relevant baseline characteristics and outcomes were extracted and compared.Of 52 PPMS studies identified, four were selected. Inclusion criteria were notably different among studies with respect to both the definition of PPMS and the requirements for the presence of disability progression at enrolment. Differences between the study populations included the baseline lesion load, pretreatment status and disease duration. The rate of disease progression may also be an important factor, as all but one of the studies included a large proportion of patients with a low progression rate. In addition, the endpoints specified could not detect progression adequately.Optimal PPMS study methods involve appropriate patient selection, especially regarding the PPMS phenotype and progression rate. Functional composite endpoints might be more sensitive than single endpoints in capturing progression.

  7. Evaluation of Study and Patient Characteristics of Clinical Studies in Primary Progressive Multiple Sclerosis: A Systematic Review

    Science.gov (United States)

    Ziemssen, T.; Rauer, S.; Stadelmann, C.; Henze, T.; Koehler, J.; Penner, I.-K.; Lang, M.; Poehlau, D.; Baier-Ebert, M.; Schieb, H.; Meuth, S.

    2015-01-01

    Background So far, clinical studies in primary progressive MS (PPMS) have failed to meet their primary efficacy endpoints. To some extent this might be attributable to the choice of assessments or to the selection of the study population. Objective The aim of this study was to identify outcome influencing factors by analyzing the design and methods of previous randomized studies in PPMS patients without restriction to intervention or comparator. Methods A systematic literature search was conducted in MEDLINE, EMBASE, BIOSIS and the COCHRANE Central Register of Controlled Trials (inception to February 2015). Keywords included PPMS, primary progressive multiple sclerosis and chronic progressive multiple sclerosis. Randomized, controlled trials of at least one year’s duration were selected if they included only patients with PPMS or if they reported sufficient PPMS subgroup data. No restrictions with respect to intervention or comparator were applied. Study quality was assessed by a biometrics expert. Relevant baseline characteristics and outcomes were extracted and compared. Results Of 52 PPMS studies identified, four were selected. Inclusion criteria were notably different among studies with respect to both the definition of PPMS and the requirements for the presence of disability progression at enrolment. Differences between the study populations included the baseline lesion load, pretreatment status and disease duration. The rate of disease progression may also be an important factor, as all but one of the studies included a large proportion of patients with a low progression rate. In addition, the endpoints specified could not detect progression adequately. Conclusion Optimal PPMS study methods involve appropriate patient selection, especially regarding the PPMS phenotype and progression rate. Functional composite endpoints might be more sensitive than single endpoints in capturing progression. PMID:26393519

  8. Genome-Wide Association Study in Dachshund: Identification of a Major Locus Affecting Intervertebral Disc Calcification

    DEFF Research Database (Denmark)

    Mogensen, Mette Sloth; Karlskov-Mortensen, Peter; Proschowsky, Helle Friis;

    2011-01-01

    Intervertebral disc calcification and herniation commonly affects Dachshund where the predisposition is caused by an early onset degenerative process resulting in disc calcification. A continuous spectrum of disc degeneration is seen within and among clog breeds, suggesting a multifactorial...... with intervertebral disc calcification in Dachshund through a genome-wide association (GWA) study. Based on thorough radiographic examinations, 48 cases with >= 6 disc calcifications or surgically treated for disc herniation and 46 controls with 0-1 disc calcifications were identified. GWA using the Illumina Canine......HD BeadChip identified a locus on chromosome 12 from 36.8 to 38.6 Mb with 36 markers reaching genome-wide significance (P-genome = 0.00001-0.026). This study suggests that a major locus on chromosome 12 harbors genetic variations affecting the development of intervertebral disc calcification in Dachshund....

  9. The Human Genome Initiative of the Department of Energy

    Science.gov (United States)

    1988-01-01

    The structural characterization of genes and elucidation of their encoded functions have become a cornerstone of modern health research, biology and biotechnology. A genome program is an organized effort to locate and identify the functions of all the genes of an organism. Beginning with the DOE-sponsored, 1986 human genome workshop at Santa Fe, the value of broadly organized efforts supporting total genome characterization became a subject of intensive study. There is now national recognition that benefits will rapidly accrue from an effective scientific infrastructure for total genome research. In the US genome research is now receiving dedicated funds. Several other nations are implementing genome programs. Supportive infrastructure is being improved through both national and international cooperation. The Human Genome Initiative of the Department of Energy (DOE) is a focused program of Resource and Technology Development, with objectives of speeding and bringing economies to the national human genome effort. This report relates the origins and progress of the Initiative.

  10. The Human Genome Initiative of the Department of Energy

    Energy Technology Data Exchange (ETDEWEB)

    None

    1988-01-01

    The structural characterization of genes and elucidation of their encoded functions have become a cornerstone of modern health research, biology and biotechnology. A genome program is an organized effort to locate and identify the functions of all the genes of an organism. Beginning with the DOE-sponsored, 1986 human genome workshop at Santa Fe, the value of broadly organized efforts supporting total genome characterization became a subject of intensive study. There is now national recognition that benefits will rapidly accrue from an effective scientific infrastructure for total genome research. In the US genome research is now receiving dedicated funds. Several other nations are implementing genome programs. Supportive infrastructure is being improved through both national and international cooperation. The Human Genome Initiative of the Department of Energy (DOE) is a focused program of Resource and Technology Development, with objectives of speeding and bringing economies to the national human genome effort. This report relates the origins and progress of the Initiative. 34 refs.

  11. 鹦鹉热嗜衣原体基因组学的研究进展%Research progress on genomics of Chlamydophila psittaci

    Institute of Scientific and Technical Information of China (English)

    黎知青

    2012-01-01

    目前,7株鹦鹉热嗜衣原体全基因组己测序完整,揭示了不同株之间的相同性与差异性.主要外膜蛋白基因、多形态膜蛋白多基因家族、Ⅲ型分泌系统基因和包涵体膜蛋白基因是鹦鹉热嗜表原体(Chlamydophila psittaci,Cps)研究的重点.对多个种株Cps基因组完整核苷酸序列测定的研究,将有助于进一步了解Cps的致病机制,寻找更好的诊断方法和防治措施,预防和控制Cps的流行.%At present, the whole genomes of seven strains Chlamydophila psittaci (Cp) have been completely se-quenced and it reveals the similarities and differences among each other. Major outer membrane protein genes, the polymorphic membrane protein multiple genes family, the type Ⅲ secretion system genes, and the inclusion membrane protein genes are the focuses of study on Chlamydophila psittaci. The studies on genome integrity nucleotide sequencing among multiple strains of Cps will help for further understanding of the pathogenesis of Cps, searching for better diagnostic methods and prevention measures, and preventing and controlling the prevalence of Cps.

  12. Studies in iodine metabolism: Progress report, July 1968-July 1969

    Energy Technology Data Exchange (ETDEWEB)

    Van Middlesworth, L.

    1987-01-01

    This document describes research on iodine metabolism conducted at the University of Tennessee, Memphis between July 1968 and July 1969. The author and his research team prepared autoradiographs of rat thyroids from individuals exposed to Iodine 125 in utero. Additional studies were conducted to determine the effect on hypothalamic lesions on iodide metabolism in rats; to evaluate an iodide-specific electrode for measuring iodide levels in blood or urine; and to study the amount of thyroxine absorption from the intestine. An analysis of bovine and sheep thyroids from eight locations provided additional information on global fallout levels. 21 figs., 2 tabs.

  13. The progress in the study of Arctic pack ice ecology

    Institute of Scientific and Technical Information of China (English)

    何剑锋; 王桂忠; 蔡明红; 李少菁

    2004-01-01

    The sea ice community plays an important role in the Arctic marine ecosystem. Because of the predicted environmental changes in the Arctic environment and specifically related to sea ice, the Arctic pack ice biota has received more attention in recent years using modern ice-breaking research vessels. Studies show that the Arctic pack ice contains a diverse biota and besides ice algae, the bacterial and protozoan biomasses can be high. Surprisingly high primary production values were observed in the pack ice of the central Arctic Ocean. Occasionally biomass maximum were discovered in the interior of the ice floes, a habitat that had been ignored in most Arctic studies. Many scientific questions, which deserve special attention, remained unsolved due to logistic limitations and the sea ice characteristics. Little is know about the pack ice community in the central Arctic Ocean. Almost no data exists from the pack ice zone for the winter season. Concerning the abundance of bacteria and protozoa, more studies are needed to understand the microbial network within the ice and its role in material and energy flows. The response of the sea ice biota to global change will impact the entire Arctic marine ecosystem and a long-term monitoring program is needed. The techniques, that are applied to study the sea ice biota and the sea ice ecology, should be improved.

  14. Comparison of buccal and blood-derived canine DNA, either native or whole genome amplified, for array-based genome-wide association studies

    Directory of Open Access Journals (Sweden)

    Lawley Cynthia

    2011-06-01

    Full Text Available Abstract Background The availability of array-based genotyping platforms for single nucleotide polymorphisms (SNPs for the canine genome has expanded the opportunities to undertake genome-wide association (GWA studies to identify the genetic basis for Mendelian and complex traits. Whole blood as the source of high quality DNA is undisputed but often proves impractical for collection of the large numbers of samples necessary to discover the loci underlying complex traits. Further, many countries prohibit the collection of blood from dogs unless medically necessary thereby restricting access to critical control samples from healthy dogs. Alternate sources of DNA, typically from buccal cytobrush extractions, while convenient, have been suggested to have low yield and perform poorly in GWA. Yet buccal cytobrushes provide a cost-effective means of collecting DNA, are readily accepted by dog owners, and represent a large resource base in many canine genetics laboratories. To increase the DNA quantities, whole genome amplification (WGA can be performed. Thus, the present study assessed the utility of buccal-derived DNA as well as whole genome amplification in comparison to blood samples for use on the most recent iteration of the canine HD SNP array (Illumina. Findings In both buccal and blood samples, whether whole genome amplified or not, 97% of the samples had SNP call rates in excess of 80% indicating that the vast majority of the SNPs would be suitable to perform association studies regardless of the DNA source. Similarly, there were no significant differences in marker intensity measurements between buccal and blood samples for copy number variations (CNV analysis. Conclusions All DNA samples assayed, buccal or blood, native or whole genome amplified, are appropriate for use in array-based genome-wide association studies. The concordance between subsets of dogs for which both buccal and blood samples, or those samples whole genome amplified, was

  15. Moving image analysis to the cloud: A case study with a genome-scale tomographic study

    Science.gov (United States)

    Mader, Kevin; Stampanoni, Marco

    2016-01-01

    Over the last decade, the time required to measure a terabyte of microscopic imaging data has gone from years to minutes. This shift has moved many of the challenges away from experimental design and measurement to scalable storage, organization, and analysis. As many scientists and scientific institutions lack training and competencies in these areas, major bottlenecks have arisen and led to substantial delays and gaps between measurement, understanding, and dissemination. We present in this paper a framework for analyzing large 3D datasets using cloud-based computational and storage resources. We demonstrate its applicability by showing the setup and costs associated with the analysis of a genome-scale study of bone microstructure. We then evaluate the relative advantages and disadvantages associated with local versus cloud infrastructures.

  16. Moving image analysis to the cloud: A case study with a genome-scale tomographic study

    Energy Technology Data Exchange (ETDEWEB)

    Mader, Kevin [4Quant Ltd., Switzerland & Institute for Biomedical Engineering at University and ETH Zurich (Switzerland); Stampanoni, Marco [Institute for Biomedical Engineering at University and ETH Zurich, Switzerland & Swiss Light Source at Paul Scherrer Institut, Villigen (Switzerland)

    2016-01-28

    Over the last decade, the time required to measure a terabyte of microscopic imaging data has gone from years to minutes. This shift has moved many of the challenges away from experimental design and measurement to scalable storage, organization, and analysis. As many scientists and scientific institutions lack training and competencies in these areas, major bottlenecks have arisen and led to substantial delays and gaps between measurement, understanding, and dissemination. We present in this paper a framework for analyzing large 3D datasets using cloud-based computational and storage resources. We demonstrate its applicability by showing the setup and costs associated with the analysis of a genome-scale study of bone microstructure. We then evaluate the relative advantages and disadvantages associated with local versus cloud infrastructures.

  17. Recent progresses at IENGF on studies on quantum information

    Science.gov (United States)

    Brida, G.; Cagliero, E.; Genovese, M.; Gramegna, M.; Predazzi, E.

    2005-08-01

    In this proceeding we present the most recent studies performed at IEN "Galileo Ferraris" on quantum information by using quantum optical states. After a general summary of the most recent studies, among them we will present in some details the results of two recent experiments. The first was addressed to tomographic reconstruction of a quantum state by using an innovative theoretical scheme based on a variable quantum efficiency of the detector. This scheme has been applied to Fock (PDC heralded photons), coherent (attenuated laser beam) and thermal states, for which experimental results will be presented. The second was pointed to experimentally investigate the effects of fibre propagation of PDC light produced in a type II crystal and, in particular, to the restoration of entanglement due to wave packet dispersion. Also in this case we will present and discuss our most recent data. Finally, we will shortly acknowledge of realisation of a heralded photon source with strong spectral selection.

  18. Introduction. Progress in Earth science and climate studies.

    Science.gov (United States)

    Thompson, J Michael T

    2008-12-28

    In this introductory paper, I review the 'visions of the future' articles prepared by top young scientists for the second of the two Christmas 2008 Triennial Issues of Phil. Trans. R. Soc.A, devoted respectively to astronomy and Earth science. Topics covered in the Earth science issue include: trace gases in the atmosphere; dynamics of the Antarctic circumpolar current; a study of the boundary between the Earth's rocky mantle and its iron core; and two studies of volcanoes and their plumes. A final section devoted to ecology and climate covers: the mathematical modelling of plant-soil interactions; the effects of the boreal forests on the Earth's climate; the role of the past palaeoclimate in testing and calibrating today's numerical climate models; and the evaluation of these models including the quantification of their uncertainties.

  19. Nuclear structure studies. Progress report, [1988--1994

    Energy Technology Data Exchange (ETDEWEB)

    Walters, W.B.

    1993-07-31

    In this report, newly initiated work at the FMA is described where the use of double-sided strip detectors for charged particle spectroscopy on nuclides near the proton drip line has been investigated. Half lives for proton emitting nuclides have been determined with improved uncertainties. Several sections report on the results of studies of model parameters in the Z = 50 region for even-even nuclides, for odd-mass nuclides and for odd-odd nuclides. Other studies are reported for nuclear orientation in Br and for structure of Pr-147 which lies in a transition zone between reflection-asymmetric, spherical, and prolate nuclides. And there is a section in which the positions of the single Particle levels in the A = 100 region are discussed.

  20. Recent progress in vortex studies by tunneling spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Kohen, A. [Institut des NanoSciences de Paris, UMR7588 au CNRS, Universite Paris 6 and Paris 7, 140 rue de Lourmel, 75015 Paris (France)]. E-mail: Amir.Kohen@insp.jussieu.fr; Cren, T. [Institut des NanoSciences de Paris, UMR7588 au CNRS, Universite Paris 6 and Paris 7, 140 rue de Lourmel, 75015 Paris (France); Noat, Y. [Institut des NanoSciences de Paris, UMR7588 au CNRS, Universite Paris 6 and Paris 7, 140 rue de Lourmel, 75015 Paris (France); Proslier, T. [Institut des NanoSciences de Paris, UMR7588 au CNRS, Universite Paris 6 and Paris 7, 140 rue de Lourmel, 75015 Paris (France); Giubileo, F. [Physics Department and INFM-SUPERMAT Laboratory, University of Salerno, via S. Allende, 84081 Baronissi (SA) (Italy); Bobba, F. [Physics Department and INFM-SUPERMAT Laboratory, University of Salerno, via S. Allende, 84081 Baronissi (SA) (Italy); Cucolo, A.M. [Physics Department and INFM-SUPERMAT Laboratory, University of Salerno, via S. Allende, 84081 Baronissi (SA) (Italy); Zhigadlo, N. [Solid State Physics Laboratory, ETH Zurich, CH-8093 Zurich (Switzerland); Kazakov, S.M. [Solid State Physics Laboratory, ETH Zurich, CH-8093 Zurich (Switzerland); Karpinski, J. [Solid State Physics Laboratory, ETH Zurich, CH-8093 Zurich (Switzerland); Sacks, W. [Institut des NanoSciences de Paris, UMR7588 au CNRS, Universite Paris 6 and Paris 7, 140 rue de Lourmel, 75015 Paris (France); Roditchev, D. [Institut des NanoSciences de Paris, UMR7588 au CNRS, Universite Paris 6 and Paris 7, 140 rue de Lourmel, 75015 Paris (France)

    2006-05-15

    Among the methods used to study the vortex state in superconductors, scanning tunneling spectroscopy (STS), is unique in its ability to measure in real space the variations in the local quasiparticle density of states. Thus, as opposed to magnetic imaging, STS gives direct access to the coherence length rather than to the penetration length. Here we discuss two novel methods which enhance the capabilities of STS as a tool for the study of the vortex state. In the first one, called Lazy Fisherman [A. Kohen et al., Appl. Phys. Lett. 86 (2005) 212503], the scanning tunneling microscope's tip is kept fixed at a selected location while the vortices are being moved by varying the applied magnetic field. By continuously acquiring the local tunneling conductance spectra, dI/dV(V), we detect the changes in the local density of states under the tip due to the vortex motion. With no need for scanning, the method permits one to extend the study of vortices to samples in which scanning is difficult or even impossible due to surface non-uniformity and allows one to detect faster vortex dynamics. To illustrate the approach we study single crystal samples of MgB{sub 2}. In the second STS method, we replace the commonly used normal metal STM tip by a superconducting (SC) tip which we produce either by mechanically breaking a Nb wire under vacuum in the STM chamber [A. Kohen et al., Physica C 49 (2005) 18] or by gluing a piece of a crystal of MgB{sub 2} [F. Giubileo et al., Phys. Rev. Lett. 87 (2001) 177008]. The use of a SC tip enhances the energy resolution of STS in comparison to that obtained with a normal metal tip. The method is illustrated by using Nb and MgB{sub 2} tips to perform a simultaneous topographic and spectroscopic imaging on 2H-NbSe{sub 2}.

  1. Thorium assessment study quarterly progress report, third quarter fiscal 1977

    Energy Technology Data Exchange (ETDEWEB)

    Spiewak, I.; Bartine, D. E.; Burns, T. J.; Cleveland, J. C.; Thomas, W. E.; White, J. R.

    1977-09-30

    The objective of the program described is to contribute to the ongoing assessment of the potential role of thorium fuel cycles for alleviating safeguards concerns. Scenarios include (1) no fuel recycle permitted, (2) fuel recycle permitted only in secure regions (''energy parks'') with denatured (chemically non-separable) fuels only outside these regions, and (3) no limits on fuel recycle. A further objective is to provide nuclear mass balance data on HTGRs required by ERDA contractors for comparative cost-benefit studies.

  2. Progress in studies of gene therapy for Huntington's disease

    Directory of Open Access Journals (Sweden)

    JIN Fan-ying

    2012-06-01

    Full Text Available Huntington's disease (HD is a kind of inherited neurodegenerative disorder characterized by movement problems, cognitive decline and psychiatry disturbance. HD is caused by mutation in gene IT -15 involving the expansion of a trinucleotide (CAG repeat encoding glutamine, which leads to abnormal conformation of huntingtin (Htt protein and finally emerge cytotoxic functions. Currently, HD remains a fatal untreatable disease. Gene therapy for HD discussed in this review is under preclinical studies. Silencing of mutant IT-15 via RNA interference (RNAi or antisense oligonucleotide (ASO has shown some effectiveness in mouse model studies. Increasing the clearance of mutant Htt protein could be achieved by viral-mediated delivery of anti-Htt intrabodies (iAbs or induction of autophagy, and beneficial results have been observed. Ectopic expression of neurotrophic factors, such as nerve growth factor (NGF and brain-derived neurotrophic factor (BDNF, mediated either by viral vectors or transplantation of genetically modified cells, has also been proved to be effective. Other gene-modifying methods aiming at correction of transcriptional dysregulation by histone modification, activation of endogenous neural stem cells, and normalization of calcium signaling and mitochondrial function, are also under intensive research. Gene therapy for Huntington's disease is promising, yet a long way remains from preclinical studies to clinical trials.

  3. A genome assembly-integrated dog 1 Mb BAC microarray: a cytogenetic resource for canine cancer studies and comparative genomic analysis.

    Science.gov (United States)

    Thomas, R; Duke, S E; Karlsson, E K; Evans, A; Ellis, P; Lindblad-Toh, K; Langford, C F; Breen, M

    2008-01-01

    Molecular cytogenetic studies have been instrumental in defining the nature of numerical and structural chromosome changes in human cancers, but their significance remains to be fully understood. The emergence of high quality genome assemblies for several model organisms provides exciting opportunities to develop novel genome-integrated molecular cytogenetic resources that now permit a comparative approach to evaluating the relevance of tumor-associated chromosome aberrations, both within and between species. We have used the dog genome sequence assembly to identify a framework panel of 2,097 bacterial artificial chromosome (BAC) clones, selected at intervals of approximately one megabase. Each clone has been evaluated by multicolor fluorescence in situ hybridization (FISH) to confirm its unique cytogenetic location in concordance with its reported position in the genome assembly, providing new information on the organization of the dog genome. This panel of BAC clones also represents a powerful cytogenetic resource with numerous potential applications. We have used the clone set to develop a genome-wide microarray for comparative genomic hybridization (aCGH) analysis, and demonstrate its application in detection of tumor-associated DNA copy number aberrations (CNAs) including single copy deletions and amplifications, regional aneuploidy and whole chromosome aneuploidy. We also show how individual clones selected from the BAC panel can be used as FISH probes in direct evaluation of tumor karyotypes, to verify and explore CNAs detected using aCGH analysis. This cytogenetically validated, genome integrated BAC clone panel has enormous potential for aiding gene discovery through a comparative approach to molecular oncology.

  4. Privacy-preserving genome-wide association studies on cloud environment using fully homomorphic encryption.

    Science.gov (United States)

    Lu, Wen-Jie; Yamada, Yoshiji; Sakuma, Jun

    2015-01-01

    Developed sequencing techniques are yielding large-scale genomic data at low cost. A genome-wide association study (GWAS) targeting genetic variations that are significantly associated with a particular disease offers great potential for medical improvement. However, subjects who volunteer their genomic data expose themselves to the risk of privacy invasion; these privacy concerns prevent efficient genomic data sharing. Our goal is to presents a cryptographic solution to this problem. To maintain the privacy of subjects, we propose encryption of all genotype and phenotype data. To allow the cloud to perform meaningful computation in relation to the encrypted data, we use a fully homomorphic encryption scheme. Noting that we can evaluate typical statistics for GWAS from a frequency table, our solution evaluates frequency tables with encrypted genomic and clinical data as input. We propose to use a packing technique for efficient evaluation of these frequency tables. Our solution supports evaluation of the D' measure of linkage disequilibrium, the Hardy-Weinberg Equilibrium, the χ2 test, etc. In this paper, we take χ2 test and linkage disequilibrium as examples and demonstrate how we can conduct these algorithms securely and efficiently in an outsourcing setting. We demonstrate with experimentation that secure outsourcing computation of one χ2 test with 10, 000 subjects requires about 35 ms and evaluation of one linkage disequilibrium with 10, 000 subjects requires about 80 ms. With appropriate encoding and packing technique, cryptographic solutions based on fully homomorphic encryption for secure computations of GWAS can be practical.

  5. Recent Progress in the Study of Dinosaur Eggs in China

    Institute of Scientific and Technical Information of China (English)

    WANG Qiang; WANG Xiaolin; ZHAO Zikui

    2010-01-01

    @@ Dinosaur eggs are a special type of vertebrate fossils.Despite their varied shapes,all dinosaur eggs are composed of eggshells,though the thickness of the shell may also vary.Dinosaur eggshells consist primarily of the mineral calcite(calcium carbonate).By studying dinosaur eggs,we can infer the reproductive system and behavior of dinosaurs and even the palaeoenvironment,palaeoclimate,palaeoecology in which they lived.Moreover,dinosaur eggs are useful for stratigraphic division and correlation as well as paleobiogeographic interpretations.

  6. Progresses on study of epigenetics in neurodegenerative disorders

    Directory of Open Access Journals (Sweden)

    SONG Cheng-yuan

    2013-07-01

    Full Text Available Epigenetics refer to the collective heritable changes in phenotype due to processes that arise independently of primary DNA sequence. It is comprised of DNA methylation, histone proteins modifications, non-coding and so on. Aberrant epigenetic modifications are involved in the development of neurodegenerative disorders. Recently, many epigenetics-based medications have been developed and provided us new strategies for treatment of those diseases, including Alzheimer's disease, Parkinson's disease and Huntington's disease. In this review, we would like to summarize the recent studies of epigenetic modification in neurodegeneration, mainly focusing on DNA methylation and histone acetylation and exploring the possibility of using epigenetics-based therapeutics to treat neurodegenerative disorders.

  7. Dynamic probe selection for studying microbial transcriptome with high-density genomic tiling microarrays

    Directory of Open Access Journals (Sweden)

    Chen Tsute

    2010-02-01

    Full Text Available Abstract Background Current commercial high-density oligonucleotide microarrays can hold millions of probe spots on a single microscopic glass slide and are ideal for studying the transcriptome of microbial genomes using a tiling probe design. This paper describes a comprehensive computational pipeline implemented specifically for designing tiling probe sets to study microbial transcriptome profiles. Results The pipeline identifies every possible probe sequence from both forward and reverse-complement strands of all DNA sequences in the target genome including circular or linear chromosomes and plasmids. Final probe sequence lengths are adjusted based on the maximal oligonucleotide synthesis cycles and best isothermality allowed. Optimal probes are then selected in two stages - sequential and gap-filling. In the sequential stage, probes are selected from sequence windows tiled alongside the genome. In the gap-filling stage, additional probes are selected from the largest gaps between adjacent probes that have already been selected, until a predefined number of probes is reached. Selection of the highest quality probe within each window and gap is based on five criteria: sequence uniqueness, probe self-annealing, melting temperature, oligonucleotide length, and probe position. Conclusions The probe selection pipeline evaluates global and local probe sequence properties and selects a set of probes dynamically and evenly distributed along the target genome. Unique to other similar methods, an exact number of non-redundant probes can be designed to utilize all the available probe spots on any chosen microarray platform. The pipeline can be applied to microbial genomes when designing high-density tiling arrays for comparative genomics, ChIP chip, gene expression and comprehensive transcriptome studies.

  8. Research progress in studies on the coalbed gas geochemistry

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The current situation of geochemical studies on coalbed gas is reviewed in this paper. Generally, coalbed gas is compositionally dominated by methane with δ13C1 values ranging approximately from - 80‰ to - 10‰. However, few isotopic studies have been carried out on other components of coalbed gas except for hydrogen and carbon dioxide, whose δDCH4 values available for utilization vary from - 333‰ to - 117‰, and δ13CCO2 values from -29.4‰ to + 18.6‰. Two major types of coalbed gas, thermogenic gas and secondary biogenic gas, have been identified, and there are also some other classification criteria. Compared with conventional natural gases,coalbed gas has a wide distribution range of δ13C1 andδ13CCO2 values, especially possessing some extremely heavy values. Current problems that remain unsolved in the coalbed gas geochemistry include the variation mechanism, controlling factors and application of carbon and hydrogen isotopes of methane, the relation between the values of δ13C1 and Ro, the systematic classification scheme and criterion of genetic types, and the application of the coalbed gas geochemistry in evaluating target districts of the coalbed gas exploration.

  9. Progress in cognitive neuroscientific studies of visual awareness

    Institute of Scientific and Technical Information of China (English)

    Qi Li; Haiyan Geng

    2009-01-01

    The psychological and neural mechanisms of consciousness are among the most baffling problems in cognitive neuroscience. In this field, visual awareness is a topic that has been largely investigated, due to easy manipulation and measurable effects. The present arti-cle begins with the phenomena of dissociations between visual awareness and visual stimulus, visual awareness and visual attention, as well as visual awareness and vision-guided behavior, along with the corresponding experimental evidence. Furthermore, the neural mechanism of visual awareness is also discussed. It has been generally believed that visual awareness is the function of higher-order cerebral areas; however, recent discoveries have demonstrated that feedback from higher- to lower-order cortex areas is necessary for generating consciousness. The present article presents an in-depth analysis regarding this feedback process, and exploring its relation-ship with the generation and mechanisms of consciousness. Finally, theoretical controversies and discrepancies, as well as result con-flicts from various studies, have been collected, compared and discussed. Because the field of consciousness continues to be an extremely mysterious and complicated psychological phenomenon, there is a great need for further studies to explore and clarify this topic.

  10. Progress in Nanoscale Studies of Hydrogen Reactions in Construction Materials

    Science.gov (United States)

    Schweitzer, J. S.; Livingston, R. A.; Cheung, J.; Rolfs, C.; Becker, H.-W.; Kubsky, S.; Spillane, T.; Zickefoose, J.; Castellote, M.; Bengtsson, N.; Galan, I.; de Viedma, P. G.; Brendle, S.; Bumrongjaroen, W.; Muller, I.

    Nuclear resonance reaction analysis (NRRA) has been applied to measure the nanoscale distribution of hydrogen with depth in the hydration of cementitious phases. This has provided a better understanding of the mechanisms and kinetics of cement hydration during the induction period that is critical to improved concrete technology. NRRA was also applied to measure the hydrogen depth profiles in other materials used in concrete construction such as fly ash and steel. By varying the incident beam energy one measures a profile with a depth resolution of a few nanometers. Time-resolved measurements are achieved by stopping the chemical reactions at specific times. Effects of temperature, sulfate concentration, accelerators and retarders, and superplasticizers have been investigated. Hydration of fly ashes has been studied with synthetic glass specimens whose chemical compositions are modeled on those of actual fly ashes. A combinatorial chemistry approach was used where glasses of different compositions are hydrated in various solutions for a fixed time. The resulting hydrogen depth profiles show significant differences in hydrated phases, rates of depth penetration and amount of surface etching. Hydrogen embrittlement of steel was studied on slow strain rate specimens under different corrosion potentials.

  11. Great Basin paleoenvironmental studies project; Technical progress report: First quarter (January--August 1993)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    Project goals, project tasks, progress on tasks, and problems encountered are described and discussed for each of the studies that make up the Great Basin Paleoenvironmental Studies Project for Yucca Mountain. These studies are: Paleobotany, Paleofauna, Geomorphology, and Transportation. Budget summaries are also given for each of the studies and for the overall project.

  12. Genomic profiling of breast cancer.

    Science.gov (United States)

    Pandey, Anjita; Singh, Alok Kumar; Maurya, Sanjeev Kumar; Rai, Rajani; Tewari, Mallika; Kumar, Mohan; Shukla, Hari S

    2009-05-01

    Genome study provides significant changes in the advancement of molecular diagnosis and treatment in Breast cancer. Several recent critical advances and high-throughput techniques identified the genomic trouble and dramatically accelerated the pace of research in preventing and curing this malignancy. Tumor-suppressor genes, proto-oncogenes, DNA-repair genes, carcinogen-metabolism genes are critically involved in progression of breast cancer. We reviewed imperative finding in breast genetics, ongoing work to segregate further susceptible genes, and preliminary studies on molecular profiling.

  13. Optimizing the creation of base populations for aquaculture breeding programs using phenotypic and genomic data and its consequences on genetic progress.

    Science.gov (United States)

    Fernández, Jesús; Toro, Miguel Á; Sonesson, Anna K; Villanueva, Beatriz

    2014-01-01

    The success of an aquaculture breeding program critically depends on the way in which the base population of breeders is constructed since all the genetic variability for the traits included originally in the breeding goal as well as those to be included in the future is contained in the initial founders. Traditionally, base populations were created from a number of wild strains by sampling equal numbers from each strain. However, for some aquaculture species improved strains are already available and, therefore, mean phenotypic values for economically important traits can be used as a criterion to optimize the sampling when creating base populations. Also, the increasing availability of genome-wide genotype information in aquaculture species could help to refine the estimation of relationships within and between candidate strains and, thus, to optimize the percentage of individuals to be sampled from each strain. This study explores the advantages of using phenotypic and genome-wide information when constructing base populations for aquaculture breeding programs in terms of initial and subsequent trait performance and genetic diversity level. Results show that a compromise solution between diversity and performance can be found when creating base populations. Up to 6% higher levels of phenotypic performance can be achieved at the same level of global diversity in the base population by optimizing the selection of breeders instead of sampling equal numbers from each strain. The higher performance observed in the base population persisted during 10 generations of phenotypic selection applied in the subsequent breeding program.

  14. Optimizing the creation of base populations for aquaculture breeding programs using phenotypic and genomic data and its consequences on genetic progress

    Directory of Open Access Journals (Sweden)

    Jesús eFernández

    2014-11-01

    Full Text Available The success of an aquaculture breeding program critically depends on the way in which the base population of breeders is constructed since all the genetic variability for the traits included originally in the breeding goal as well as those to be included in the future is contained in those initial founders. Traditionally base populations were created from a number of wild strains by sampling equal numbers from each strain. However, for some aquaculture species improved strains are already available and therefore, mean phenotypic values for economically important traits can be used as a criterion to optimize the sampling when creating base populations. Also, the increasing availability of genome-wide genotype information in aquaculture species could help to refine the estimation of relationships within and between candidate strains and, thus, to optimize the percentage of individuals to be sampled from each strain. This study explores the advantages of using phenotypic and genome-wide information when constructing base populations for aquaculture breeding programs in terms of initial and subsequent trait performance and genetic diversity level. Results show that a compromise solution between diversity and performance can be found when creating base populations. Up to 6% higher levels of phenotypic performance can be achieved at the same level of global diversity in the base population by optimizing the selection of breeders instead of sampling equal numbers from each strain. The higher performance observed in the base population persisted during ten generations of phenotypic selection applied in the subsequent breeding program.

  15. MSR Studies in the Progress Towards Diamond Electronics

    Energy Technology Data Exchange (ETDEWEB)

    Connell, S. H., E-mail: connell@src.wits.ac.za [University of the Witwatersrand, Schonland Research Institute for Nuclear Sciences (South Africa); Machi, I. Z. [University of South Africa, Physics Department (South Africa); Bharuth-Ram, K. [University of KwaZulu Natal, School of Pure and Applied Physics (South Africa)

    2004-12-15

    The recent development of device quality synthetic diamond dramatically increases the potential of diamond as a wide band gap semiconductor. A remaining obstacle is the lack of shallow n-type dopants. Molecular dopant systems have been shown theoretically to lead to the shallowing of levels in the band gap. Some of these systems involve defect-hydrogen complexes. This, and other phenomena, motivate the study of the chemistry and dynamics of hydrogen in diamond. Much information on this topic has been obtained from Muon Spin Rotation (MSR) experiments. These experiments view the muonium (Mu {identical_to} {mu}{sup +}e{sup -}) atom as a light chemical analogue of hydrogen. Data on isolated muonium in diamond is reviewed, and evidence on formation of N-Mu-N (a shallow dopant candidate), the trapping of Mu at B-dopants, and fast quantum diffusion of muonium are discussed.

  16. Idaho Steelhead Monitoring and Evaluation Studies : Annual Progress Report 2007.

    Energy Technology Data Exchange (ETDEWEB)

    Copeland, Timothy; Putnam, Scott

    2008-12-01

    The goal of Idaho Steelhead Monitoring and Evaluation Studies is to collect monitoring data to evaluate wild and natural steelhead populations in the Clearwater and Salmon river drainages. During 2007, intensive population data were collected in Fish Creek (Lochsa River tributary) and Rapid River (Little Salmon River tributary); extensive data were collected in other selected spawning tributaries. Weirs were operated in Fish Creek and Rapid River to estimate adult escapement and to collect samples for age determination and genetic analysis. Snorkel surveys were conducted in Fish Creek, Rapid River, and Boulder Creek (Little Salmon River tributary) to estimate parr density. Screw traps were operated in Fish Creek, Rapid River, Secesh River, and Big Creek to estimate juvenile emigrant abundance, to tag fish for survival estimation, and to collect samples for age determination and genetic analysis. The estimated wild adult steelhead escapement in Fish Creek was 81 fish and in Rapid River was 32 fish. We estimate that juvenile emigration was 24,127 fish from Fish Creek; 5,632 fish from Rapid River; and 43,674 fish from Big Creek. The Secesh trap was pulled for an extended period due to wildfires, so we did not estimate emigrant abundance for that location. In cooperation with Idaho Supplementation Studies, trap tenders PIT tagged 25,618 steelhead juveniles at 18 screw trap sites in the Clearwater and Salmon river drainages. To estimate age composition, 143 adult steelhead and 5,082 juvenile steelhead scale samples were collected. At the time of this report, 114 adult and 1,642 juvenile samples have been aged. Project personnel collected genetic samples from 122 adults and 839 juveniles. We sent 678 genetic samples to the IDFG Eagle Fish Genetics Laboratory for analysis. Water temperature was recorded at 37 locations in the Clearwater and Salmon river drainages.

  17. Comparative genomics study for identification of putative drug targets in Salmonella typhi Ty2.

    Science.gov (United States)

    Batool, Nisha; Waqar, Maleeha; Batool, Sidra

    2016-01-15

    Typhoid presents a major health concern in developing countries with an estimated annual infection rate of 21 million. The disease is caused by Salmonella typhi, a pathogenic bacterium acquiring multiple drug resistance. We aim to identify proteins that could prove to be putative drug targets in the genome of S. typhi str. Ty2. We employed comparative and subtractive genomics to identify targets that are absent in humans and are essential to S. typhi Ty2. We concluded that 46 proteins essential to pathogen are absent in the host genome. Filtration on the basis of drug target prioritization singled out 20 potentially therapeutic targets. Their absence in the host and specificity to S. typhi Ty2 makes them ideal targets for treating typhoid in Homo sapiens. 3D structures of two of the final target enzymes, MurA and MurB have been predicted via homology modeling which are then used for a docking study.

  18. Use of DBD-FISH for the study of cervical cancer progression.

    Science.gov (United States)

    Cortés-Gutiérrez, Elva I; Fernández, Jose Luis; Dávila-Rodríguez, Martha I; López-Fernández, Carmen; Gosálvez, Jaime

    2015-01-01

    DNA breakage detection-fluorescence in situ hybridization (DBD-FISH) is a procedure to detect and quantify DNA breaks in single cells, either in the whole genome or within specific DNA sequences. This methodology combines microgel embedding of cells and DNA unwinding procedures with the power of FISH coupled to digital image analysis. Cells trapped within an agarose matrix are lysed and immersed in an alkaline unwinding solution that produces single-stranded DNA motifs beginning at the ends of internal DNA strand breaks. After neutralization, the microgel is dehydrated and the cells are incubated with fluorescently labeled DNA probes. The amount of hybridized probe at a target sequence correlates with the amount of single-stranded DNA generated during the unwinding step, which is in turn proportional to the degree of local DNA breakage. A general view of the technique is provided, emphasizing its versatility for evaluating the association between DNA damage and progressive stages of cervical neoplasia.

  19. Chipping away at a mountain: Genomic studies in Common Variable Immunodeficiency

    Science.gov (United States)

    Keller, Michael D; Jyonouchi, Soma

    2012-01-01

    Common variable immunodeficiency (CVID) represents one of the most frequently diagnosed disorders of the immune system. Though several causative and associated genes have been identified, the origins of most cases remain unknown. Diagnostic delay is common due to the gradual evolution and wide spectrum of phenotypes, which can include autoimmune disease, enteropathy, and lung disease. A recent genome wide array identified novel gene associations with CVID, and also showed that identification of a genetic signature via a Support Vector Machine algorithm may be a powerful diagnostic tool. Studies utilizing whole genome or exome sequencing have also met with success in identifying new causes of CVID in subgroups of patients. PMID:23201919

  20. A genome-wide association study of pulmonary function measures in the Framingham Heart Study.

    Directory of Open Access Journals (Sweden)

    Jemma B Wilk

    2009-03-01

    Full Text Available The ratio of forced expiratory volume in one second to forced vital capacity (FEV(1/FVC is a measure used to diagnose airflow obstruction and is highly heritable. We performed a genome-wide association study in 7,691 Framingham Heart Study participants to identify single-nucleotide polymorphisms (SNPs associated with the FEV(1/FVC ratio, analyzed as a percent of the predicted value. Identified SNPs were examined in an independent set of 835 Family Heart Study participants enriched for airflow obstruction. Four SNPs in tight linkage disequilibrium on chromosome 4q31 were associated with the percent predicted FEV(1/FVC ratio with p-values of genome-wide significance in the Framingham sample (best p-value = 3.6e-09. One of the four chromosome 4q31 SNPs (rs13147758; p-value 2.3e-08 in Framingham was genotyped in the Family Heart Study and produced evidence of association with the same phenotype, percent predicted FEV(1/FVC (p-value = 2.0e-04. The effect estimates for association in the Framingham and Family Heart studies were in the same direction, with the minor allele (G associated with higher FEV(1/FVC ratio levels. Results from the Family Heart Study demonstrated that the association extended to FEV(1 and dichotomous airflow obstruction phenotypes, particularly among smokers. The SNP rs13147758 was associated with the percent predicted FEV(1/FVC ratio in independent samples from the Framingham and Family Heart Studies producing a combined p-value of 8.3e-11, and this region of chromosome 4 around 145.68 megabases was associated with COPD in three additional populations reported in the accompanying manuscript. The associated SNPs do not lie within a gene transcript but are near the hedgehog-interacting protein (HHIP gene and several expressed sequence tags cloned from fetal lung. Though it is unclear what gene or regulatory effect explains the association, the region warrants further investigation.

  1. The Oxytricha trifallax macronuclear genome: a complex eukaryotic genome with 16,000 tiny chromosomes.

    Directory of Open Access Journals (Sweden)

    Estienne C Swart

    Full Text Available The macronuclear genome of the ciliate Oxytricha trifallax displays an extreme and unique eukaryotic genome architecture with extensive genomic variation. During sexual genome development, the expressed, somatic macronuclear genome is whittled down to the genic portion of a small fraction (∼5% of its precursor "silent" germline micronuclear genome by a process of "unscrambling" and fragmentation. The tiny macronuclear "nanochromosomes" typically encode single, protein-coding genes (a small portion, 10%, encode 2-8 genes, have minimal noncoding regions, and are differentially amplified to an average of ∼2,000 copies. We report the high-quality genome assembly of ∼16,000 complete nanochromosomes (∼50 Mb haploid genome size that vary from 469 bp to 66 kb long (mean ∼3.2 kb and encode ∼18,500 genes. Alternative DNA fragmentation processes ∼10% of the nanochromosomes into multiple isoforms that usually encode complete genes. Nucleotide diversity in the macronucleus is very high (SNP heterozygosity is ∼4.0%, suggesting that Oxytricha trifallax may have one of the largest known effective population sizes of eukaryotes. Comparison to other ciliates with nonscrambled genomes and long macronuclear chromosomes (on the order of 100 kb suggests several candidate proteins that could be involved in genome rearrangement, including domesticated MULE and IS1595-like DDE transposases. The assembly of the highly fragmented Oxytricha macronuclear genome is the first completed genome with such an unusual architecture. This genome sequence provides tantalizing glimpses into novel molecular biology and evolution. For example, Oxytricha maintains tens of millions of telomeres per cell and has also evolved an intriguing expansion of telomere end-binding proteins. In conjunction with the micronuclear genome in progress, the O. trifallax macronuclear genome will provide an invaluable resource for investigating programmed genome rearrangements, complementing

  2. PROGRESS IN STUDIES ON ICE ACCUMULATION IN RIVER BENDS

    Institute of Scientific and Technical Information of China (English)

    WANG Jun; CHEN Pang-pang; SUI Jue-yi

    2011-01-01

    River ice is an important hydraulic element in temperate and polar environments and would affect hydrodynamic conditions of rivers through changes both in the boundary conditions and the thermal regime.The river bend has been reported as the common location for the initiation of ice jams because the water flow along a river bend is markedly affected by the channel curvature.In this article,the experimental studies about the ice accumulation in a river bend are reviewed.Based on experiments conducted so far,the criteria for the formation of ice jams in the river bend,the mechanisms of the ice accumulation in the river bend and the thickness profile of the ice accumulation in the river bend are discussed.The k- ε two-equation turbulence model is used to simulate the ice accumulation under an ice cover along a river bend.A formula is proposed for describing the deformation of the ice jam bottom.Our results indicate that all simulated thickness of the ice accumulation agrees reasonably well with the measured thickness of the ice accumulation in the laboratory.

  3. [Study of heavy-flavored particles]. Part 1, Progress report

    Energy Technology Data Exchange (ETDEWEB)

    1993-04-01

    The program of physics analysis using CLEO II data is reported. A statistically significant measurement was made of the isospin mass splitting of the {Sigma}{sub c}{sup +} with respect to the {Sigma}{sub c}{sup o} and {Sigma}{sub c}{sup ++}. This result is based on first observation of the {Sigma}{sub c}{sup +} in the decay mode {Lambda}{sub c}{sup +}{pi}{sup 0}. Many new decay modes of the charmed baryon {Lambda}{sub c}{sup +} were studied. Several new decay modes of {xi}{sub c}`s. Some preliminary results on 3 new modes of {Omega}{sub c}{sup 0} decay are reported. In the area of B-meson decay into baryons, were observed conclusively the decays B {yields} {Sigma}{sub c}{sup 0} and {Sigma}{sub c}{sup ++}. From about 1500 events corresponding to B {yields} {Lambda}{sub c}{sup +}X reconstruction of exclusive final states of the form {Lambda}{sub c}{sup +}(n{pi}) was started. A comprehensive investigation of particle identification using both the time-of-flight and dE/dx systems was made. Measurement of pion, kaon and proton identification efficiencies have been made, corresponding to several different selection criteria. Measurements of corresponding pion probabilities to fake kaons nd protons have also been made.

  4. [Genomic approach to pathophysiology of rheumatoid arthritis].

    Science.gov (United States)

    Yamada, Ryo

    2012-11-01

    Genetic studies identified multiple genes and polymorphisms that increase risk to develop rheumatoid arthritis. Genomic approach is characterized with its integrative style using mathematical and statistical models. Its main targets include (1)combinatorial effect of multiple genetic and environmental factors, (2)heterogeneity of pathological states and its individuality, and (3)their chronological heterogeneity. Genomic approach will clarify pathophysiology of various diseases along with the progresses in molecular biology and other researches on individual molecules.

  5. A genome-wide study of recombination rate variation in Bartonella henselae

    Directory of Open Access Journals (Sweden)

    Guy Lionel

    2012-05-01

    Full Text Available Abstract Background Rates of recombination vary by three orders of magnitude in bacteria but the reasons for this variation is unclear. We performed a genome-wide study of recombination rate variation among genes in the intracellular bacterium Bartonella henselae, which has among the lowest estimated ratio of recombination relative to mutation in prokaryotes. Results The 1.9 Mb genomes of B. henselae strains IC11, UGA10 and Houston-1 genomes showed only minor gene content variation. Nucleotide sequence divergence levels were less than 1% and the relative rate of recombination to mutation was estimated to 1.1 for the genome overall. Four to eight segments per genome presented significantly enhanced divergences, the most pronounced of which were the virB and trw gene clusters for type IV secretion systems that play essential roles in the infection process. Consistently, multiple recombination events were identified inside these gene clusters. High recombination frequencies were also observed for a gene putatively involved in iron metabolism. A phylogenetic study of this gene in 80 strains of Bartonella quintana, B. henselae and B. grahamii indicated different population structures for each species and revealed horizontal gene transfers across Bartonella species with different host preferences. Conclusions Our analysis has shown little novel gene acquisition in B. henselae, indicative of a closed pan-genome, but higher recombination frequencies within the population than previously estimated. We propose that the dramatically increased fixation rate for recombination events at gene clusters for type IV secretion systems is driven by selection for sequence variability.

  6. Genome-wide association study of sepsis in extremely premature infants.

    Science.gov (United States)

    Srinivasan, Lakshmi; Page, Grier; Kirpalani, Haresh; Murray, Jeffrey C; Das, Abhik; Higgins, Rosemary D; Carlo, Waldemar A; Bell, Edward F; Goldberg, Ronald N; Schibler, Kurt; Sood, Beena G; Stevenson, David K; Stoll, Barbara J; Van Meurs, Krisa P; Johnson, Karen J; Levy, Joshua; McDonald, Scott A; Zaterka-Baxter, Kristin M; Kennedy, Kathleen A; Sánchez, Pablo J; Duara, Shahnaz; Walsh, Michele C; Shankaran, Seetha; Wynn, James L; Cotten, C Michael

    2017-09-01

    To identify genetic variants associated with sepsis (early-onset and late-onset) using a genome-wide association (GWA) analysis in a cohort of extremely premature infants. Previously generated GWA data from the Neonatal Research Network's anonymised genomic database biorepository of extremely premature infants were used for this study. Sepsis was defined as culture-positive early-onset or late-onset sepsis or culture-proven meningitis. Genomic and whole-genome-amplified DNA was genotyped for 1.2 million single-nucleotide polymorphisms (SNPs); 91% of SNPs were successfully genotyped. We imputed 7.2 million additional SNPs. p Values and false discovery rates (FDRs) were calculated from multivariate logistic regression analysis adjusting for gender, gestational age and ancestry. Target statistical value was p<10(-5). Secondary analyses assessed associations of SNPs with pathogen type. Pathway analyses were also run on primary and secondary end points. Data from 757 extremely premature infants were included: 351 infants with sepsis and 406 infants without sepsis. No SNPs reached genome-wide significance levels (5×10(-8)); two SNPs in proximity to FOXC2 and FOXL1 genes achieved target levels of significance. In secondary analyses, SNPs for ELMO1, IRAK2 (Gram-positive sepsis), RALA, IMMP2L (Gram-negative sepsis) and PIEZO2 (fungal sepsis) met target significance levels. Pathways associated with sepsis and Gram-negative sepsis included gap junctions, fibroblast growth factor receptors, regulators of cell division and interleukin-1-associated receptor kinase 2 (p values<0.001 and FDR<20%). No SNPs met genome-wide significance in this cohort of extremely low birthweight infants; however, areas of potential association and pathways meriting further study were identified. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  7. The challenges of genome-wide interaction studies: Lessons to learn from the analysis of HDL blood levels

    NARCIS (Netherlands)

    E.M. van Leeuwen (Elisa); F.A.S. Smouter (Françoise A.S.); T. Kam-Thong (Tony); N. Karbalai (Nazanin); G.D. Smith; T.B. Harris (Tamara); L.J. Launer (Lenore); C.M. Sitlani (Colleen); G. Li (Guo); J. Brody (Jennifer); J.C. Bis (Joshua); C.C. White (Charles); A. Jaiswal (Alok); B.A. Oostra (Ben); A. Hofman (Albert); F. Rivadeneira Ramirez (Fernando); A.G. Uitterlinden (André); E.A. Boerwinkle (Eric); C. Ballantyne (Christie); V. Gudnason (Vilmundur); B.M. Psaty (Bruce); L.A. Cupples (Adrienne); M.-R. Jarvelin (Marjo-Riitta); S. Ripatti (Samuli); A.J. Isaacs (Aaron); B. Müller-Myhsok (B.); L.C. Karssen (Lennart); C.M. van Duijn (Cock)

    2014-01-01

    textabstractGenome-wide association studies (GWAS) have revealed 74 single nucleotide polymorphisms (SNPs) associated with high-density lipoprotein cholesterol (HDL) blood levels. This study is, to our knowledge, the first genome-wide interaction study (GWIS) to identify SNP6SNP interactions associa

  8. Genetic susceptibility to male infertility: news from genome-wide association studies.

    Science.gov (United States)

    Aston, K I

    2014-05-01

    A thorough understanding of the genetic basis of male infertility has eluded researchers in spite of significant efforts to identify novel genetic causes of the disease, particularly over the past decade. Approximately half of male factor infertility cases have no known cause; however, it is likely that the majority of idiopathic male factor infertility cases have some unidentified genetic basis. Well-established genetic causes of male infertility are limited to Y chromosome microdeletions and Klinefelter's syndrome, together accounting for 10-20% of cases of severe spermatogenic failure. In addition to these, several genetic polymorphisms have been demonstrated to be significantly associated with male infertility. The discovery of new genetic associations with male infertility has been hampered by two primary factors. First, most studies are underpowered because of insufficient sample size and ethnic and phenotypic heterogeneity. Second, most studies evaluate a single gene, an approach that is very inefficient in the context of male infertility, considering that many hundreds of genes are involved in the process of testicular development and spermatogenesis. Significant recent advances in microarray and next-generation sequencing technologies have enabled the application of whole-genome approaches to the study of male infertility. We recently performed a pilot genome-wide association study (GWAS) for severe spermatogenic failure, and several additional male infertility GWAS have since been published. More recently, genomic microarray tools have been applied to the association of copy number variants with male infertility. These studies are beginning to shed additional light on the genetic architecture of male infertility, and whole-genome studies have proven effective in identifying novel genetic causes of the disease. This review will discuss some of the recent findings of these whole-genome studies as well as future directions for this research that will likely

  9. Recent Progress in Studies of Climate Change in China

    Institute of Scientific and Technical Information of China (English)

    REN Guoyu; DING Yihui; ZHAO Zongci; ZHENG Jingyun; WU Tongwen; TANG Guoli; XU Ying

    2012-01-01

    An overview of basic research on climate change in recent years in China is presented. In the past 100 years in China,average annual mean surface air temperature (SAT) has increased at a rate ranging from 0.03℃ (10 yr)-1 to 0.12℃ (10 yr)-1.This warming is more evident in northern China and is more significant in winter and spring.In the past 50 years in China,at least 27% of the average annual warming has been caused by urbanization.Overall,no significant trends have been detected in annual and/or summer precipitation in China on a whole for the past 100 years or 50 years. Both increases and decreases in frequencies of major extreme climate events have been observed for the past 50 years. The frequencies of extreme temperature events have generally displayed a consistent pattern of change across the country,while the frequencies of extreme precipitation events have shown only regionally and seasonally significant trends.The frequency of tropical cyclone landfall decreased slightly,but the frequency of sand/dust storms decreased significantly.Proxy records indicate that the annual mean SAT in the past a few decades is the highest in the past 400-500 years in China,but it may not have exceeded the highest level of the Medieval Warm Period (1000-1300 AD).Proxy records also indicate that droughts and floods in eastern China have been characterized by continuously abnormal rainfall periods,with the frequencies of extreme droughts and floods in the 20th century most likely being near the average levels of the past 2000 years.The attribution studies suggest that increasing greenhouse gas (GHG) concentrations in the atmosphere are likely to be a main factor for the observed surface warming nationwide.The Yangtze River and Huaihe River basins underwent a cooling trend in summer over the past 50 years,which might have been caused by increased aerosol concentrations and cloud cover.However,natural climate variability might have been a main driver for the mean and

  10. Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization

    NARCIS (Netherlands)

    Bonnelykke, Klaus; Matheson, Melanie C.; Pers, Tune H.; Granell, Raquel; Strachan, David P.; Alves, Alexessander Couto; Linneberg, Allan; Curtin, John A.; Warrington, Nicole M.; Standl, Marie; Kerkhof, Marjan; Jonsdottir, Ingileif; Bukvic, Blazenka K.; Kaakinen, Marika; Sleimann, Patrick; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Schramm, Katharina; Baltic, Svetlana; Kreiner-Moller, Eskil; Simpson, Angela; St Pourcain, Beate; Coin, Lachlan; Hui, Jennie; Walters, Eugene H.; Tiesler, Carla M. T.; Duffy, David L.; Jones, Graham; Ring, Susan M.; McArdle, Wendy L.; Price, Loren; Robertson, Colin F.; Pekkanen, Juha; Tang, Clara S.; Thiering, Elisabeth; Montgomery, Grant W.; Hartikainen, Anna-Liisa; Dharmage, Shyamali C.; Husemoen, Lise L.; Herder, Christian; Kemp, John P.; Elliot, Paul; James, Alan; Waldenberger, Melanie; Abramson, Michael J.; Fairfax, Benjamin P.; Knight, Julian C.; Gupta, Ramneek; Thompson, Philip J.; Holt, Patrick; Sly, Peter; Hirschhorn, Joel N.; Blekic, Mario; Weidinger, Stephan; Hakonarsson, Hakon; Stefansson, Kari; Heinrich, Joachim; Postma, Dirkje S.; Custovic, Adnan; Pennell, Craig E.; Jarvelin, Marjo-Riitta; Koppelman, Gerard H.; Timpson, Nicholas; Ferreira, Manuel A.; Bisgaard, Hans; Henderson, A. John

    2013-01-01

    Allergen-specific immunoglobulin E (present in allergic sensitization) has a central role in the pathogenesis of allergic disease. We performed the first large-scale genome-wide association study (GWAS) of allergic sensitization in 5,789 affected individuals and 10,056 controls and followed up the t

  11. Meta-analysis of genome-wide linkage studies in BMI and obesity

    NARCIS (Netherlands)

    Saunders, Catherine L.; Chiodini, Benedetta D.; Sham, Pak; Lewis, Cathryn M.; Abkevich, Victor; Adeyemo, Adebowale A.; de Andrade, Mariza; Arya, Rector; Berenson, Gerald S.; Blangero, John; Boehnke, Michael; Borecki, Ingrid B.; Chagnon, Yvon C.; Chen, Wei; Comuzzie, Anthony G.; Deng, Hong-Wen; Duggirala, Ravindranath; Feitosa, Mary F.; Froguel, Philippe; Hanson, Robert L.; Hebebrand, Johannes; Huezo-Dias, Patricia; Kissebah, Ahmed H.; Li, Weidong; Luke, Amy; Martin, Lisa J.; Nash, Matthew; Ohman, Muena; Palmer, Lyle J.; Peltonen, Leena; Perola, Markus; Price, R. Arlen; Redline, Susan; Srinivasan, Sathanur R.; Stern, Michael P.; Stone, Steven; Stringham, Heather; Turner, Stephen; Wijmenga, Cisca; Collier, David A.

    Objective: The objective was to provide an overall assessment of genetic linkage data of BMI and BMI-defined obesity using a nonparametric genome scan meta-analysis. Research Methods and Procedures: We identified 37 published studies containing data on over 31,000 individuals from more than >10,000

  12. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma

    NARCIS (Netherlands)

    Chambers, John C; Zhang, Weihua; Sehmi, Joban; Li, Xinzhong; Wass, Mark N; Van der Harst, Pim; Holm, Hilma; Sanna, Serena; Kavousi, Maryam; Baumeister, Sebastian E; Coin, Lachlan J; Deng, Guohong; Gieger, Christian; Heard-Costa, Nancy L; Hottenga, Jouke-Jan; Kühnel, Brigitte; Kumar, Vinod; Lagou, Vasiliki; Liang, Liming; Luan, Jian'an; Vidal, Pedro Marques; Mateo Leach, Irene; O'Reilly, Paul F; Peden, John F; Rahmioglu, Nilufer; Soininen, Pasi; Speliotes, Elizabeth K; Yuan, Xin; Thorleifsson, Gudmar; Alizadeh, Behrooz Z; Atwood, Larry D; Borecki, Ingrid B; Brown, Morris J; Charoen, Pimphen; Cucca, Francesco; Das, Debashish; de Geus, Eco J C; Dixon, Anna L; Döring, Angela; Ehret, Georg; Eyjolfsson, Gudmundur I; Farrall, Martin; Forouhi, Nita G; Friedrich, Nele; Goessling, Wolfram; Gudbjartsson, Daniel F; Harris, Tamara B; Hartikainen, Anna-Liisa; Heath, Simon; Hirschfield, Gideon M; Hofman, Albert; Homuth, Georg; Hyppönen, Elina; Janssen, Harry L A; Johnson, Toby; Kangas, Antti J; Kema, Ido P; Kühn, Jens P; Lai, Sandra; Lathrop, Mark; Lerch, Markus M; Li, Yun; Liang, T Jake; Lin, Jing-Ping; Loos, Ruth J F; Martin, Nicholas G; Moffatt, Miriam F; Montgomery, Grant W; Munroe, Patricia B; Musunuru, Kiran; Nakamura, Yusuke; O'Donnell, Christopher J; Olafsson, Isleifur; Penninx, Brenda W; Pouta, Anneli; Prins, Bram P; Prokopenko, Inga; Puls, Ralf; Ruokonen, Aimo; Savolainen, Markku J; Schlessinger, David; Schouten, Jeoffrey N L; Seedorf, Udo; Sen-Chowdhry, Srijita; Siminovitch, Katherine A; Smit, Johannes H; Spector, Timothy D; Tan, Wenting; Teslovich, Tanya M; Tukiainen, Taru; Uitterlinden, Andre G; Van der Klauw, Melanie M; Vasan, Ramachandran S; Wallace, Chris; Wallaschofski, Henri; Wichmann, H-Erich; Willemsen, Gonneke; Würtz, Peter; Xu, Chun; Yerges-Armstrong, Laura M; Abecasis, Goncalo R; Ahmadi, Kourosh R; Boomsma, Dorret I; Caulfield, Mark; Cookson, William O; van Duijn, Cornelia M; Froguel, Philippe; Matsuda, Koichi; McCarthy, Mark I; Meisinger, Christa; Mooser, Vincent; Pietiläinen, Kirsi H; Schumann, Gunter; Snieder, Harold; Sternberg, Michael J E; Stolk, Ronald P; Thomas, Howard C; Thorsteinsdottir, Unnur; Uda, Manuela; Waeber, Gérard; Wareham, Nicholas J; Waterworth, Dawn M; Watkins, Hugh; Whitfield, John B; Witteman, Jacqueline C M; Wolffenbuttel, Bruce H R; Fox, Caroline S; Ala-Korpela, Mika; Stefansson, Kari; Vollenweider, Peter; Völzke, Henry; Schadt, Eric E; Scott, James; Järvelin, Marjo-Riitta; Elliott, Paul; Kooner, Jaspal S

    2011-01-01

    Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190))

  13. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    DEFF Research Database (Denmark)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.

    2015-01-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from ...

  14. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    NARCIS (Netherlands)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.; Duncan, Laramie; Parikshak, Neelroop N.; Newhouse, Stephen; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Posthuma, Danielle; Nurnberger, John I.; Lee, S. Hong; Faraone, Stephen V.; Perlis, Roy H.; Mowry, Bryan J.; Thapar, Anita; Goddard, Michael E.; Witte, John S.; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A.; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E.; Asherson, Philip; Azevedo, Maria H.; Backlund, Lena; Badner, Judith A.; Bailey, Anthony J.; Banaschewski, Tobias; Barchas, Jack D.; Barnes, Michael R.; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayes, Monica; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B.; Black, Donald W.; Blackwood, Douglas H. R.; Bloss, Cinnamon S.; Boehnke, Michael; Boomsma, Dorret I.; Breuer, Rene; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G.; Buitelaar, Jan K.; Bunney, William E.; Buxbaum, Joseph D.; Byerley, William F.; Byrne, Enda M.; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M.; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Mattheisen, Manuel; Cloninger, C. Robert; Collier, David A.; Cook, Edwin H.; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H.; Craig, David W.; Craig, Ian W.; Crosbie, Jennifer; Cuccaro, Michael L.; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; De Geus, Eco J.; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J.; Doyle, Alysa E.; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P.; Edenberg, Howard J.; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E.; Ferrier, I. Nicol; Flicldnger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B.; Freitag, Christine M.; Friedl, Marion; Frisen, Louise; Gailagher, Louise; Gejman, Pablo V.; Georgieva, Lyudmila; Gershon, Elliot S.; Giegling, Ina; Gill, Michael; Gordon, Scott D.; Gordon-Smith, Katherine; Green, Elaine K.; Greenwood, Tiffany A.; Grice, Dorothy E.; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; De Haan, Lieuwe; Haines, Jonathan L.; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P.; Hamshere, Marian L.; Hansen, Thomas F.; Hartmann, Annette M.; Hautzinger, Martin; Heath, Andrew C.; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hipolito, Maria; Hoefels, Susanne; Holsboer, Florian; Hoogendijk, Witte J.; Hottenga, Jouke-Jan; Hultman, Christina M.; Hus, Vanessa; Ingason, Andres; Ising, Marcus; Jamain, Stephane; Jones, Edward G.; Jones, Ian; Jones, Lisa; Tzeng, Jung-Ying; Kaehler, Anna K.; Kahn, Rene S.; Kandaswamy, Radhika; Keller, Matthew C.; Kennedy, James L.; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K.; Klauck, Sabine M.; Klei, Lambertus; Knowles, James A.; Kohli, Martin A.; Koller, Daniel L.; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landen, Mikael; Laengstroem, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B.; Leboyer, Marion; Ledbetter, David H.; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F.; Lewis, Cathryn M.; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A.; Lin, Dan-Yu; Linszen, Don H.; Liu, Chunyu; Lohoff, Falk W.; Loo, Sandra K.; Lord, Catherine; Lowe, Jennifer K.; Lucae, Susanne; MacIntyre, Donald J.; Madden, Pamela A. F.; Maestrini, Elena; Magnusson, Patrik K. E.; Mahon, Pamela B.; Maier, Wolfgang; Malhotra, Anil K.; Mane, Shrikant M.; Martin, Christa L.; Martin, Nicholas G.; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A.; McGhee, Kevin A.; McGough, James J.; McGrath, Patrick J.; McGuffin, Peter; McInnis, Melvin G.; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W.; McMahon, Francis J.; McMahon, William M.; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E.; Meier, Sandra; Melle, Ingrid; Meng, Fan; Meyer, Jobst; Middeldorp, Christel M.; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P.; Montgomery, Grant W.; Moran, Jennifer L.; Moreno-De-Luca, Daniel; Morken, Gunnar; Morris, Derek W.; Morrow, Eric M.; Moskvina, Valentina; Muglia, Pierandrea; Muehleisen, Thomas W.; Muir, Walter J.; Mueller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M.; Myin-Germeys, Inez; Neale, Michael C.; Nelson, Stan F.; Nievergelt, Caroline M.; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A.; Noethen, Markus M.; Nwulia, Evaristus A.; Nyholt, Dale R.; Oades, Robert D.; Olincy, Ann; Oliveira, Guiomar; Olsen, Line; Ophoff, Roel A.; Osby, Urban; Owen, Michael J.; Palotie, Aarno; Parr, Jeremy R.; Paterson, Andrew D.; Pato, Carlos N.; Pato, Michele T.; Penninx, Brenda W.; Pergadia, Michele L.; Pericak-Vance, Margaret A.; Pickard, Benjamin S.; Pimm, Jonathan; Piven, Joseph; Potash, James B.; Poustka, Fritz; Propping, Peter; Puri, Vinay; Quested, Digby J.; Quinn, Emma M.; Ramos-Quiroga, Josep Antoni; Rasmussen, Henrik B.; Raychaudhuri, Soumya; Rehnstroem, Karola; Reif, Andreas; Ribases, Marta; Rice, John P.; Rietschel, Marcella; Roeder, Kathryn; Roeyers, Herbert; Rothenberger, Aribert; Rouleau, Guy; Ruderfer, Douglas; Rujescu, Dan; Sanders, Alan R.; Sanders, Stephan J.; Santangelo, Susan L.; Sergeant, Joseph A.; Schachar, Russell; Schalling, Martin; Schatzberg, Alan F.; Scheftner, William A.; Schellenberg, Gerard D.; Scherer, Stephen W.; Schork, Nicholas J.; Schulze, Thomas G.; Schumacher, Johannes; Schwarz, Markus; Scolnick, Edward; Scott, Laura J.; Shi, Jianxin; Shilling, Paul D.; Shyn, Stanley I.; Silverman, Jeremy M.; Slager, Susan L.; Smalley, Susan L.; Smit, Johannes H.; Smith, Erin N.; Sonuga-Barke, Edmund J. S.; Cair, David St.; State, Matthew; Steffens, Michael; Steinhausen, Hans-Christoph; Strauss, John S.; Strohmaier, Jana; Stroup, T. Scott; Sutdiffe, James S.; Szatmari, Peter; Szelinger, Szabocls; Thirumalai, Srinivasa; Thompson, Robert C.; Todorov, Alexandre A.; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; Van den Oord, Edwin J. C. G.; Van Grootheest, Gerard; Van Os, Jim; Vicente, Astrid M.; Vieland, Veronica J.; Vincent, John B.; Visscher, Peter M.; Walsh, Christopher A.; Wassink, Thomas H.; Watson, Stanley J.; Weissman, Myrna M.; Werge, Thomas; Wienker, Thomas F.; Wijsman, Ellen M.; Willemsen, Gonneke; Williams, Nigel; Willsey, A. Jeremy; Witt, Stephanie H.; Xu, Wei; Young, Allan H.; Yu, Timothy W.; Zammit, Stanley; Zandi, Peter P.; Zhang, Peng; Zitman, Frans G.; Zoellner, Sebastian; Devlin, Bernie; Kelsoe, John R.; Sklar, Pamela; Daly, Mark J.; O'Donovan, Michael C.; Craddock, Nicholas; Kendler, Kenneth S.; Weiss, Lauren A.; Wray, Naomi R.; Zhao, Zhaoming; Geschwind, Daniel H.; Sullivan, Patrick F.; Smoller, Jordan W.; Holmans, Peter A.; Breen, Gerome

    2015-01-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from ove

  15. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci

    NARCIS (Netherlands)

    Stahl, Eli A.; Raychaudhuri, Soumya; Remmers, Elaine F.; Xie, Gang; Eyre, Stephen; Thomson, Brian P.; Li, Yonghong; Kurreeman, Fina A. S.; Zhernakova, Alexandra; Hinks, Anne; Guiducci, Candace; Chen, Robert; Alfredsson, Lars; Amos, Christopher I.; Ardlie, Kristin G.; Barton, Anne; Bowes, John; Brouwer, Elisabeth; Burtt, Noel P.; Catanese, Joseph J.; Coblyn, Jonathan; Coenen, Marieke J. H.; Costenbader, Karen H.; Criswell, Lindsey A.; Crusius, J. Bart A.; Cui, Jing; de Bakker, Paul I. W.; De Jager, Philip L.; Ding, Bo; Emery, Paul; Flynn, Edward; Harrison, Pille; Hocking, Lynne J.; Huizinga, Tom W. J.; Kastner, Daniel L.; Ke, Xiayi; Lee, Annette T.; Liu, Xiangdong; Martin, Paul; Morgan, Ann W.; Padyukov, Leonid; Posthumus, Marcel D.; Radstake, Timothy R. D. J.; Reid, David M.; Seielstad, Mark; Seldin, Michael F.; Shadick, Nancy A.; Steer, Sophia; Tak, Paul P.; Thomson, Wendy; van der Helm-van Mil, Annette H. M.; van der Horst-Bruinsma, Irene E.; van der Schoot, C. Ellen; van Riel, Piet L. C. M.; Weinblatt, Michael E.; Wilson, Anthony G.; Wolbink, Gert Jan; Wordsworth, B. Paul; Wijmenga, Cisca; Karlson, Elizabeth W.; Toes, Rene E. M.; de Vries, Niek; Begovich, Ann B.; Worthington, Jane; Siminovitch, Katherine A.; Gregersen, Peter K.; Klareskog, Lars; Plenge, Robert M.

    2010-01-01

    To identify new genetic risk factors for rheumatoid arthritis, we conducted a genome-wide association study meta-analysis of 5,539 autoantibody-positive individuals with rheumatoid arthritis (cases) and 20,169 controls of European descent, followed by replication in an independent set of 6,768 rheum

  16. Genome-wide association study identifies 74 loci associated with educational attainment

    NARCIS (Netherlands)

    Okbay, Aysu; Beauchamp, Jonathan P.; Fontana, Mark Alan; Lee, James J.; Pers, Tune H.; Rietveld, Cornelius A.; Turley, Patrick; Chen, Guo-Bo; Emilsson, Valur; Meddens, S. Fleur W.; Oskarsson, Sven; Pickrell, Joseph K.; Thom, Kevin; Timshel, Pascal; de Vlaming, Ronald; Abdellaoui, Abdel; Ahluwalia, Tarunveer S.; Bacelis, Jonas; Baumbach, Clemens; Bjornsdottir, Gyda; Brandsma, Johannes H.; Concas, Maria Pina; Derringer, Jaime; Furlotte, Nicholas A.; Galesloot, Tessel E.; Girotto, Giorgia; Gupta, Richa; Hall, Leanne M.; Harris, Sarah E.; Hofer, Edith; Horikoshi, Momoko; Huffman, Jennifer E.; Kaasik, Kadri; Kalafati, Ioanna P.; Karlsson, Robert; Kong, Augustine; Lahti, Jari; van der Lee, Sven J.; de Leeuw, Christiaan; Lind, Penelope A.; Lindgren, Karl-Oskar; Liu, Tian; Mangino, Massimo; Marten, Jonathan; Mihailov, Evelin; Miller, Michael B.; van der Most, Peter J.; Oldmeadow, Christopher; Payton, Antony; Pervjakova, Natalia; Peyrot, Wouter J.; Qian, Yong; Raitakari, Olli; Rueedi, Rico; Salvi, Erika; Schmidt, Brge; Schraut, Katharina E.; Shi, Jianxin; Smith, Albert V.; Poot, Raymond A.; St Pourcain, Beate; Teumer, Alexander; Thorleifsson, Gudmar; Verweij, Niek; Vuckovic, Dragana; Wellmann, Juergen; Westra, Harm-Jan; Yang, Jingyun; Zhao, Wei; Zhu, Zhihong; Alizadeh, Behrooz Z.; Amin, Najaf; Bakshi, Andrew; Baumeister, Sebastian E.; Biino, Ginevra; Bonnelykke, Klaus; Boyle, Patricia A.; Campbell, Harry; Cappuccio, Francesco P.; Davies, Gail; De Neve, Jan-Emmanuel; Deloukas, Panos; Demuth, Ilja; Ding, Jun; Eibich, Peter; Eisele, Lewin; Eklund, Niina; Evans, David M.; Faul, Jessica D.; Feitosa, Mary F.; Forstner, Andreas J.; Gandin, Ilaria; Gunnarsson, Bjarni; Halldorsson, Bjarni V.; Harris, Tamara B.; Heath, Andrew C.; Hocking, Lynne J.; Holliday, Elizabeth G.; Homuth, Georg; Horan, Michael A.; Hottenga, Jouke-Jan; de Jager, Philip L.; Joshi, Peter K.; Jugessur, Astanand; Kaakinen, Marika A.; Kahonen, Mika; Kanoni, Stavroula; Keltigangas-Jarvinen, Liisa; Kiemeney, Lambertus A. L. M.; Kolcic, Ivana; Koskinen, Seppo; Kraja, Aldi T.; Kroh, Martin; Kutalik, Zoltan; Latvala, Antti; Launer, Lenore J.; Lebreton, Mael P.; Levinson, Douglas F.; Lichtenstein, Paul; Lichtner, Peter; Liewald, David C. M.; Loukola, Anu; Madden, Pamela A.; Magi, Reedik; Maki-Opas, Tomi; Marioni, Riccardo E.; Marques-Vidal, Pedro; Meddens, Gerardus A.; McMahon, George; Meisinger, Christa; Meitinger, Thomas; Milaneschi, Yusplitri; Milani, Lili; Montgomery, Grant W.; Myhre, Ronny; Nelson, Christopher P.; Nyholt, Dale R.; Ollier, William E. R.; Palotie, Aarno; Paternoster, Lavinia; Pedersen, Nancy L.; Petrovic, Katja E.; Porteous, David J.; Raikkonen, Katri; Ring, Susan M.; Robino, Antonietta; Rostapshova, Olga; Rudan, Igor; Rustichini, Aldo; Salomaa, Veikko; Sanders, Alan R.; Sarin, Antti-Pekka; Schmidt, Helena; Scott, Rodney J.; Smith, Blair H.; Smith, Jennifer A.; Staessen, Jan A.; Steinhagen-Thiessen, Elisabeth; Strauch, Konstantin; Terracciano, Antonio; Tobin, Martin D.; Ulivi, Sheila; Vaccargiu, Simona; Quaye, Lydia; van Rooij, Frank J. A.; Venturini, Cristina; Vinkhuyzen, Anna A. E.; Volker, Uwe; Volzke, Henry; Vonk, Judith M.; Waage, Johannes; Ware, Erin B.; Willemsen, Gonneke; Attia, John R.; Bennett, David A.; Berger, Klaus; Bertram, Lars; Bisgaard, Hans; Boomsma, Dorret I.; Borecki, Ingrid B.; Bultmann, Ute; Chabris, Christopher F.; Cucca, Francesco; Cusi, Daniele; Deary, Ian J.; Dedoussis, George V.; van Duijn, Cornelia M.; Eriksson, Johan G.; Franke, Barbara; Franke, Lude; Gasparini, Paolo; Gejman, Pablo V.; Gieger, Christian; Grabe, Hans-Jorgen; Gratten, Jacob; Groenen, Patrick J. F.; Gudnason, Vilmundur; van der Harst, Pim; Hayward, Caroline; Hinds, David A.; Hoffmann, Wolfgang; Hyppnen, Elina; Iacono, William G.; Jacobsson, Bo; Jarvelin, Marjo-Riitta; Jockel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L. R.; Lehtimaki, Terho; Lehrer, Steven F.; Magnusson, Patrik K. E.; Martin, Nicholas G.; McGue, Matt; Metspalu, Andres; Pendleton, Neil; Penninx, Brenda W. J. H.; Perola, Markus; Pirastu, Nicola; Pirastu, Mario; Polasek, Ozren; Posthuma, Danielle; Power, Christine; Province, Michael A.; Samani, Nilesh J.; Schlessinger, David; Schmidt, Reinhold; Sorensen, Thorkild I. A.; Spector, Tim D.; Stefansson, Kari; Thorsteinsdottir, Unnur; Thurik, A. Roy; Timpson, Nicholas J.; Tiemeier, Henning; Tung, Joyce Y.; Uitterlinden, Andre G.; Vitart, Veronique; Vollenweider, Peter; Weir, David R.; Wilson, James F.; Wright, Alan F.; Conley, Dalton C.; Krueger, Robert F.; Smith, George Davey; Hofman, Albert; Laibson, David I.; Medland, Sarah E.; Meyer, Michelle N.; Yang, Jian; Johannesson, Magnus; Visscher, Peter M.; Esko, Tonu; Koellinger, Philipp D.; Cesarini, David; Benjamin, Daniel J.

    2016-01-01

    Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals(1). Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends

  17. Novel loci associated with usual sleep duration: The CHARGE Consortium Genome-Wide Association Study

    NARCIS (Netherlands)

    Gottlieb, D.J.; Hek, K.; Chen, T.H.; Watson, N.F.; Eiriksdottir, G.; Byrne, E.M.; Cornelis, M.; Warby, S.C.; Bandinelli, S.; Cherkas, L.; Evans, D.S.; Grabe, H.J.; Lahti, J.; Li, M.; Lehtimaki, T.; Lumley, T.; Marciante, K.D.; Pérusse, L.; Psaty, B.M.; Robbins, J.; Tranah, G.J.; Vink, J.M.; Wilk, J.B.; Stafford, J.M.; Bellis, C.; Biffar, R.; Bouchard, C.; Cade, B.; Curhan, G.C.; Eriksson, J.G.; Ewert, R.; Ferrucci, L.; Fulop, T.; Gehrman, P.R.; Goodloe, R.; Harris, T.B.; Heath, A.C.; Hernandez, D.G.; Hofman, A.; Hottenga, J.J.; Hunter, D.J.; Jensen, M.K.; Johnson, A.D.; Kahonen, M.; Kao, L.; Kraft, P.; Larkin, E.K.; Lauderdale, D.S.; Luik, A.I.; Medici, M.; Montgomery, G.W.; Palotie, A.; Patel, S.R.; Pistis, G.; Porcu, E.; Quaye, L.; Raitakari, O.; Redline, S.; Rimm, E.B.; Rotter, J.I.; Smith, A.V.; Spector, T.D.; Teumer, A.; Uitterlinden, A.G.; Vohl, M.C.; Widen, E.; Willemsen, G.; Young, T.; Zhang, X.; Liu, Y.; Blangero, J.; Boomsma, D.I.; Gudnason, V.; Hu, F.; Mangino, M.; Martin, N.G.; O'Connor, G.T.; Stone, K.L.; Tanaka, T.; Viikari, J.; Gharib, S.A.; Punjabi, N.M.; Raikkonen, K.; Völzke, H.; Mignot, E.; Tiemeier, H.

    2015-01-01

    Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based

  18. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

    NARCIS (Netherlands)

    Berndt, Sonja I; Camp, Nicola J; Skibola, Christine F; Vijai, Joseph; Wang, Zhaoming; Gu, Jian; Nieters, Alexandra; Kelly, Rachel S; Smedby, Karin E; Monnereau, Alain; Cozen, Wendy; Cox, Angela; Wang, Sophia S; Lan, Qing; Teras, Lauren R; Machado, Moara; Yeager, Meredith; Brooks-Wilson, Angela R; Hartge, Patricia; Purdue, Mark P; Birmann, Brenda M; Vajdic, Claire M; Cocco, Pierluigi; Zhang, Yawei; Giles, Graham G; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Montalvan, Rebecca; Burdett, Laurie; Hutchinson, Amy; Ye, Yuanqing; Call, Timothy G; Shanafelt, Tait D; Novak, Anne J; Kay, Neil E; Liebow, Mark; Cunningham, Julie M; Allmer, Cristine; Hjalgrim, Henrik; Adami, Hans-Olov; Melbye, Mads; Glimelius, Bengt; Chang, Ellen T; Glenn, Martha; Curtin, Karen; Cannon-Albright, Lisa A; Diver, W Ryan; Link, Brian K; Weiner, George J; Conde, Lucia; Bracci, Paige M; Riby, Jacques; Arnett, Donna K; Zhi, Degui; Leach, Justin M; Holly, Elizabeth A; Jackson, Rebecca D; Tinker, Lesley F; Benavente, Yolanda; Sala, Núria; Casabonne, Delphine; Becker, Nikolaus; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; McKay, James; Staines, Anthony; Chaffee, Kari G; Achenbach, Sara J; Vachon, Celine M; Goldin, Lynn R; Strom, Sara S; Leis, Jose F; Weinberg, J Brice; Caporaso, Neil E; Norman, Aaron D; De Roos, Anneclaire J; Morton, Lindsay M; Severson, Richard K; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Masala, Giovanna; Weiderpass, Elisabete; Chirlaque, María-Dolores; Vermeulen, Roel C H|info:eu-repo/dai/nl/216532620; Travis, Ruth C; Southey, Melissa C; Milne, Roger L; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Clavel, Jacqueline; Zheng, Tongzhang; Holford, Theodore R; Villano, Danylo J; Maria, Ann; Spinelli, John J; Gascoyne, Randy D; Connors, Joseph M; Bertrand, Kimberly A; Giovannucci, Edward; Kraft, Peter; Kricker, Anne; Turner, Jenny; Ennas, Maria Grazia; Ferri, Giovanni M; Miligi, Lucia; Liang, Liming; Ma, Baoshan; Huang, Jinyan; Crouch, Simon; Park, Ju-Hyun; Chatterjee, Nilanjan; North, Kari E; Snowden, John A; Wright, Josh; Fraumeni, Joseph F; Offit, Kenneth; Wu, Xifeng; de Sanjose, Silvia; Cerhan, James R; Chanock, Stephen J; Rothman, Nathaniel; Slager, Susan L

    2016-01-01

    Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and

  19. Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

    NARCIS (Netherlands)

    Cerhan, James R.; Berndt, Sonja I.; Vijai, Joseph; Ghesquières, Hervé; McKay, James; Wang, Sophia S.; Wang, Zhaoming; Yeager, Meredith; Conde, Lucia; De Bakker, Paul I W; Nieters, Alexandra; Cox, David; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R.; De Roos, Anneclaire J.; Brooks-Wilson, Angela R.; Lan, Qing; Severi, Gianluca; Melbye, Mads; Gu, Jian; Jackson, Rebecca D.; Kane, Eleanor; Teras, Lauren R.; Purdue, Mark P.; Vajdic, Claire M.; Spinelli, John J.; Giles, Graham G.; Albanes, Demetrius; Kelly, Rachel S.; Zucca, Mariagrazia; Bertrand, Kimberly A.; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M.; Link, Brian K.; Novak, Anne J.; Dogan, Ahmet; Asmann, Yan W.; Liebow, Mark; Thompson, Carrie A.; Ansell, Stephen M.; Witzig, Thomas E.; Weiner, George J.; Veron, Amelie S.; Zelenika, Diana; Tilly, Hervé; Haioun, Corinne; Molina, Thierry Jo; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans Olov; Bracci, Paige M.; Riby, Jacques; Smith, Martyn T.; Holly, Elizabeth A.; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M.; Severson, Richard K.; Tinker, Lesley F.; North, Kari E.; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W. Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J.; Villano, Danylo J.; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R.; Kricker, Anne; Turner, Jenny; Southey, Melissa C.; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Trichopoulos, Dimitrios; Vermeulen, Roel C H; Boeing, Heiner; Tjonneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; Birmann, Brenda M.; Laden, Francine; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C H; Sampson, Joshua; Liang, Liming; Park, Ju Hyun; Chung, Charles C.; Weisenburger, Dennis D.; Chatterjee, Nilanjan; Fraumeni, Joseph F.; Slager, Susan L.; Wu, Xifeng; De Sanjose, Silvia; Smedby, Karin E.; Salles, Gilles; Skibola, Christine F.; Rothman, Nathaniel; Chanock, Stephen J.

    2014-01-01

    Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of Euro

  20. Genome-Wide Association Study of Receptive Language Ability of 12-Year-Olds

    Science.gov (United States)

    Harlaar, Nicole; Meaburn, Emma L.; Hayiou-Thomas, Marianna E.; Davis, Oliver S. P.; Docherty, Sophia; Hanscombe, Ken B.; Haworth, Claire M. A.; Price, Thomas S.; Trzaskowski, Maciej; Dale, Philip S.; Plomin, Robert

    2014-01-01

    Purpose: Researchers have previously shown that individual differences in measures of receptive language ability at age 12 are highly heritable. In the current study, the authors attempted to identify some of the genes responsible for the heritability of receptive language ability using a "genome-wide association" approach. Method: The…

  1. Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study

    DEFF Research Database (Denmark)

    Kote-Jarai, Zsofia; Olama, Ali Amin Al; Giles, Graham G

    2011-01-01

    Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of st...

  2. Genome-Wide Association Study for Response to Eimeria maxima Challenge in Broilers

    DEFF Research Database (Denmark)

    Hamzic, Edin; Bed'hom, Bertrand; Hérault, Frédéric

    Use of genetic tools for improvement of host’s response is considered as a promising complementary approach for coccidiosis control. Therefore, we performed genome wide association study (GWAS) for response to Eimeria maxima challenge in broilers. The challenge was done on 2024 Cobb500 broilers. ...

  3. Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics

    NARCIS (Netherlands)

    Lundby, Alicia; Rossin, Elizabeth J.; Steffensen, Annette B.; Acha, Moshe Ray; Newton-Cheh, Christopher; Pfeufer, Arne; Lyneh, Stacey N.; Olesen, Soren-Peter; Brunak, Soren; Ellinor, Patrick T.; Jukema, J. Wouter; Trompet, Stella; Ford, Ian; Macfarlane, Peter W.; Krijthe, Bouwe P.; Hofman, Albert; Uitterlinden, Andre G.; Stricker, Bruno H.; Nathoe, Hendrik M.; Spiering, Wilko; Daly, Mark J.; Asselbergs, Ikea W.; van der Harst, Pim; Milan, David J.; de Bakker, Paul I. W.; Lage, Kasper; Olsen, Jesper V.

    2014-01-01

    Genome-wide association studies (GWAS) have identified thousands of loci associated with complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five genes

  4. Genome-Wide Association Study of Intelligence: Additive Effects of Novel Brain Expressed Genes

    Science.gov (United States)

    Loo, Sandra K.; Shtir, Corina; Doyle, Alysa E.; Mick, Eric; McGough, James J.; McCracken, James; Biederman, Joseph; Smalley, Susan L.; Cantor, Rita M.; Faraone, Stephen V.; Nelson, Stanley F.

    2012-01-01

    Objective: The purpose of the present study was to identify common genetic variants that are associated with human intelligence or general cognitive ability. Method: We performed a genome-wide association analysis with a dense set of 1 million single-nucleotide polymorphisms (SNPs) and quantitative intelligence scores within an ancestrally…

  5. Genome-Wide Association Study of Receptive Language Ability of 12-Year-Olds

    Science.gov (United States)

    Harlaar, Nicole; Meaburn, Emma L.; Hayiou-Thomas, Marianna E.; Davis, Oliver S. P.; Docherty, Sophia; Hanscombe, Ken B.; Haworth, Claire M. A.; Price, Thomas S.; Trzaskowski, Maciej; Dale, Philip S.; Plomin, Robert

    2014-01-01

    Purpose: Researchers have previously shown that individual differences in measures of receptive language ability at age 12 are highly heritable. In the current study, the authors attempted to identify some of the genes responsible for the heritability of receptive language ability using a "genome-wide association" approach. Method: The…

  6. Genome-wide association and functional studies identify a role for IGFBP3 in hip osteoarthritis

    NARCIS (Netherlands)

    D.S. Evans (Daniel); F. Cailotto (Frederic); N. Parimi (Neeta); A.M. Valdes (Ana Maria); M.C. Castaño Betancourt (Martha); Y. Liu (Youfang); R.C. Kaplan (Robert); M. Bidlingmaier (Martin); R.S. Vasan (Ramachandran Srini); A. Teumer (Alexander); G.J. Tranah (Gregory); M.C. Nevitt (Michael); S. Cummings; E.S. Orwoll (Eric); E. Barrett-Connor (Elizabeth); J.B. Renner (Jordan); J.M. Jordan (Joanne); M. Doherty (Michael); S. Doherty (Sally); A.G. Uitterlinden (André); J.B.J. van Meurs (Joyce); T.D. Spector (Timothy); R.J. Lories (Rik); N.E. Lane

    2014-01-01

    textabstractObjectives To identify genetic associations with hip osteoarthritis (HOA), we performed a meta-analysis of genome-wide association studies (GWAS) of HOA. Methods The GWAS meta-analysis included approximately 2.5 million imputed HapMap single nucleotide polymorphisms (SNPs). HOA cases and

  7. Genome-Wide Association Study of Intelligence: Additive Effects of Novel Brain Expressed Genes

    Science.gov (United States)

    Loo, Sandra K.; Shtir, Corina; Doyle, Alysa E.; Mick, Eric; McGough, James J.; McCracken, James; Biederman, Joseph; Smalley, Susan L.; Cantor, Rita M.; Faraone, Stephen V.; Nelson, Stanley F.

    2012-01-01

    Objective: The purpose of the present study was to identify common genetic variants that are associated with human intelligence or general cognitive ability. Method: We performed a genome-wide association analysis with a dense set of 1 million single-nucleotide polymorphisms (SNPs) and quantitative intelligence scores within an ancestrally…

  8. Critical reasoning on causal inference in genome-wide linkage and association studies

    NARCIS (Netherlands)

    Li, Yang; Tesson, Bruno M.; Churchill, Gary A.; Jansen, Ritsert C.

    2010-01-01

    Genome-wide linkage and association studies of tens of thousands of clinical and molecular traits are currently underway, offering rich data for inferring causality between traits and genetic variation. However, the inference process is based on discovering subtle patterns in the correlation between

  9. Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus

    NARCIS (Netherlands)

    Radstake, Timothy R D J; Gorlova, Olga; Rueda, Blanca; Martin, Jose-Ezequiel; Alizadeh, Behrooz Z; Palomino-Morales, Rogelio; Coenen, Marieke J; Vonk, Madelon C; Voskuyl, Alexandre E; Schuerwegh, Annemie J; Broen, Jasper C; van Riel, Piet L C M; van 't Slot, Ruben; Italiaander, Annet; Ophoff, Roel A; Riemekasten, Gabriela; Hunzelmann, Nico; Simeon, Carmen P; Ortego-Centeno, Norberto; González-Gay, Miguel A; González-Escribano, María F; Airo, Paolo; van Laar, Jaap; Herrick, Ariane; Worthington, Jane; Hesselstrand, Roger; Smith, Vanessa; de Keyser, Filip; Houssiau, Fredric; Chee, Meng May; Madhok, Rajan; Shiels, Paul; Westhovens, Rene; Kreuter, Alexander; Kiener, Hans; de Baere, Elfride; Witte, Torsten; Padykov, Leonid; Klareskog, Lars; Beretta, Lorenzo; Scorza, Rafaella; Lie, Benedicte A; Hoffmann-Vold, Anna-Maria; Carreira, Patricia; Varga, John; Hinchcliff, Monique; Gregersen, Peter K; Lee, Annette T; Ying, Jun; Han, Younghun; Weng, Shih-Feng; Amos, Christopher I; Wigley, Fredrick M; Hummers, Laura; Nelson, J Lee; Agarwal, Sandeep K; Assassi, Shervin; Gourh, Pravitt; Tan, Filemon K; Koeleman, Bobby P C; Arnett, Frank C; Martin, Javier; Mayes, Maureen D

    2010-01-01

    Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs that leads to profound disability and premature death. To identify new SSc susceptibility loci, we conducted the first genome-wide association study in a population of European ancestry includ

  10. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    NARCIS (Netherlands)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.; Duncan, Laramie; Parikshak, Neelroop N.; Newhouse, Stephen; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Posthuma, Danielle; Nurnberger, John I.; Lee, S. Hong; Faraone, Stephen V.; Perlis, Roy H.; Mowry, Bryan J.; Thapar, Anita; Goddard, Michael E.; Witte, John S.; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A.; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E.; Asherson, Philip; Azevedo, Maria H.; Backlund, Lena; Badner, Judith A.; Bailey, Anthony J.; Banaschewski, Tobias; Barchas, Jack D.; Barnes, Michael R.; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayes, Monica; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B.; Black, Donald W.; Blackwood, Douglas H. R.; Bloss, Cinnamon S.; Boehnke, Michael; Boomsma, Dorret I.; Breuer, Rene; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G.; Buitelaar, Jan K.; Bunney, William E.; Buxbaum, Joseph D.; Byerley, William F.; Byrne, Enda M.; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M.; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Mattheisen, Manuel; Cloninger, C. Robert; Collier, David A.; Cook, Edwin H.; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H.; Craig, David W.; Craig, Ian W.; Crosbie, Jennifer; Cuccaro, Michael L.; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; De Geus, Eco J.; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J.; Doyle, Alysa E.; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P.; Edenberg, Howard J.; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E.; Ferrier, I. Nicol; Flicldnger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B.; Freitag, Christine M.; Friedl, Marion; Frisen, Louise; Gailagher, Louise; Gejman, Pablo V.; Georgieva, Lyudmila; Gershon, Elliot S.; Giegling, Ina; Gill, Michael; Gordon, Scott D.; Gordon-Smith, Katherine; Green, Elaine K.; Greenwood, Tiffany A.; Grice, Dorothy E.; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; De Haan, Lieuwe; Haines, Jonathan L.; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P.; Hamshere, Marian L.; Hansen, Thomas F.; Hartmann, Annette M.; Hautzinger, Martin; Heath, Andrew C.; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hipolito, Maria; Hoefels, Susanne; Holsboer, Florian; Hoogendijk, Witte J.; Hottenga, Jouke-Jan; Hultman, Christina M.; Hus, Vanessa; Ingason, Andres; Ising, Marcus; Jamain, Stephane; Jones, Edward G.; Jones, Ian; Jones, Lisa; Tzeng, Jung-Ying; Kaehler, Anna K.; Kahn, Rene S.; Kandaswamy, Radhika; Keller, Matthew C.; Kennedy, James L.; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K.; Klauck, Sabine M.; Klei, Lambertus; Knowles, James A.; Kohli, Martin A.; Koller, Daniel L.; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landen, Mikael; Laengstroem, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B.; Leboyer, Marion; Ledbetter, David H.; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F.; Lewis, Cathryn M.; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A.; Lin, Dan-Yu; Linszen, Don H.; Liu, Chunyu; Lohoff, Falk W.; Loo, Sandra K.; Lord, Catherine; Lowe, Jennifer K.; Lucae, Susanne; MacIntyre, Donald J.; Madden, Pamela A. F.; Maestrini, Elena; Magnusson, Patrik K. E.; Mahon, Pamela B.; Maier, Wolfgang; Malhotra, Anil K.; Mane, Shrikant M.; Martin, Christa L.; Martin, Nicholas G.; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A.; McGhee, Kevin A.; McGough, James J.; McGrath, Patrick J.; McGuffin, Peter; McInnis, Melvin G.; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W.; McMahon, Francis J.; McMahon, William M.; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E.; Meier, Sandra; Melle, Ingrid; Meng, Fan; Meyer, Jobst; Middeldorp, Christel M.; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P.; Montgomery, Grant W.; Moran, Jennifer L.; Moreno-De-Luca, Daniel; Morken, Gunnar; Morris, Derek W.; Morrow, Eric M.; Moskvina, Valentina; Muglia, Pierandrea; Muehleisen, Thomas W.; Muir, Walter J.; Mueller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M.; Myin-Germeys, Inez; Neale, Michael C.; Nelson, Stan F.; Nievergelt, Caroline M.; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A.; Noethen, Markus M.

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from

  11. A mega-analysis of genome-wide association studies for major depressive disorder

    NARCIS (Netherlands)

    Sullivan, Patrick F.; Daly, Mark J.; Ripke, Stephan; Lewis, Cathryn M.; Lin, Dan-Yu; Wray, Naomi R.; Neale, Benjamin; Levinson, Douglas F.; Breen, Gerome; Byrne, Enda M.; Wray, Naomi R.; Levinson, Douglas F.; Rietschel, Marcella; Hoogendijk, Witte; Ripke, Stephan; Sullivan, Patrick F.; Hamilton, Steven P.; Levinson, Douglas F.; Lewis, Cathryn M.; Ripke, Stephan; Weissman, Myrna M.; Wray, Naomi R.; Breuer, Rene; Cichon, Sven; Degenhardt, Franziska; Frank, Josef; Gross, Magdalena; Herms, Stefan; Hoefels, Susanne; Maier, Wolfgang; Mattheisen, Manuel; Noeethen, Markus M.; Rietschel, Marcella; Schulze, Thomas G.; Steffens, Michael; Treutlein, Jens; Boomsma, Dorret I.; De Geus, Eco J.; Hoogendijk, Witte; Hottenga, Jouke Jan; Jung-Ying, Tzeng; Lin, Dan-Yu; Middeldorp, Christel M.; Nolen, Willem A.; Penninx, Brenda P.; Smit, Johannes H.; Sullivan, Patrick F.; van Grootheest, Gerard; Willemsen, Gonneke; Zitman, Frans G.; Coryell, William H.; Knowles, James A.; Lawson, William B.; Levinson, Douglas F.; Potash, James B.; Scheftner, William A.; Shi, Jianxin; Weissman, Myrna M.; Holsboer, Florian; Muglia, Pierandrea; Tozzi, Federica; Blackwood, Douglas H. R.; Boomsma, Dorret I.; De Geus, Eco J.; Hottenga, Jouke Jan; MacIntyre, Donald J.; McIntosh, Andrew; McLean, Alan; Middeldorp, Christel M.; Penninx, Brenda P.; Ripke, Stephan; Smit, Johannes H.; Sullivan, Patrick F.; van Grootheest, Gerard; Willemsen, Gonneke; Zitman, Frans G.; van den Oord, Edwin J. C. G.; Holsboer, Florian; Lucae, Susanne; Binder, Elisabeth; Mueller-Myhsok, Bertram; Ripke, Stephan; Czamara, Darina; Kohli, Martin A.; Ising, Marcus; Uhr, Manfred; Bettecken, Thomas; Barnes, Michael R.; Breen, Gerome; Craig, Ian W.; Farmer, Anne E.; Lewis, Cathryn M.; McGuffin, Peter; Muglia, Pierandrea; Byrne, Enda; Gordon, Scott D.; Heath, Andrew C.; Henders, Anjali K.; Hickie, Ian B.; Madden, Pamela A. F.; Martin, Nicholas G.; Montgomery, Grant M.; Nyholt, Dale R.; Pergadia, Michele L.; Wray, Naomi R.; Hamilton, Steven P.; McGrath, Patrick J.; Shyn, Stanley I.; Slager, Susan L.; Oskarsson, Hoegni; Sigurdsson, Engilbert; Stefansson, Hreinn; Stefansson, Kari; Steinberg, Stacy; Thorgeirsson, Thorgeir; Levinson, Douglas F.; Potash, James B.; Shi, Jianxin; Weissman, Myrna M.; Guipponi, Michel; Lewis, Glyn; O'Donovan, Michael; Tansey, Katherine E.; Uher, Rudolf; Coryell, William H.; Knowles, James A.; Lawson, William B.; Levinson, Douglas F.; Potash, James B.; Scheftner, William A.; Shi, Jianxin; Weissman, Myrna M.; Castro, Victor M.; Churchill, Susanne E.; Fava, Maurizio; Gainer, Vivian S.; Gallagher, Patience J.; Goryachev, Sergey; Iosifescu, Dan V.; Kohane, Isaac S.; Murphy, Shawn N.; Perlis, Roy H.; Smoller, Jordan W.; Weilburg, Jeffrey B.; Kutalik, Zoltan; Preisig, Martin; Grabe, Hans J.; Nauck, Matthias; Schulz, Andrea; Teumer, Alexander; Voelzke, Henry; Landen, Mikael; Lichtenstein, Paul; Magnusson, Patrik; Pedersen, Nancy; Viktorin, Alexander

    Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X

  12. Single-tube linear DNA amplification for genome-wide studies using a few thousand cells

    NARCIS (Netherlands)

    Shankaranarayanan, P.; Mendoza-Parra, M.A.; Gool, van W.; Trindade, L.M.; Gronemeyer, H.

    2012-01-01

    Linear amplification of DNA (LinDA) by T7 polymerase is a versatile and robust method for generating sufficient amounts of DNA for genome-wide studies with minute amounts of cells. LinDA can be coupled to a great number of global profiling technologies. Indeed, chromatin immunoprecipitation coupled

  13. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function

    NARCIS (Netherlands)

    D.B. Hancock (Dana); M. Eijgelsheim (Mark); J.B. Wilk (Jemma); S.A. Gharib (Sina); L.R. Loehr (Laura); K. Marciante (Kristin); N. Franceschini (Nora); Y.M.T.A. van Durme; T.H. Chen; R.G. Barr (Graham); M.B. Schabath (Matthew); D.J. Couper (David); G.G. Brusselle (Guy); B.M. Psaty (Bruce); P. Tikka-Kleemola (Päivi); J.I. Rotter (Jerome); A.G. Uitterlinden (André); A. Hofman (Albert); N.M. Punjabi (Naresh); F. Rivadeneira Ramirez (Fernando); A.C. Morrison (Alanna); P.L. Enright (Paul); K.E. North (Kari); S.R. Heckbert (Susan); T. Lumley (Thomas); B.H.Ch. Stricker (Bruno); G.T. O'Connor (George); S.J. London (Stephanie)

    2010-01-01

    textabstractSpirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV1) and it

  14. Genome-wide association studies (GWAS) and their importance in asthma

    National Research Council Canada - National Science Library

    García-Sánchez, A; Isidoro-García, M; García-Solaesa, V; Sanz, C; Hernández-Hernández, L; Padrón-Morales, J; Lorente-Toledano, F; Dávila, I

    ...: the so-called genome-wide association studies (GWAS). The first GWAS was published in 2007, and described a new locus associated to asthma in chromosome 17q12-q21, involving the ORMDL3, GSDMB and ZPBP2 genes...

  15. Genome-wide association study identifies four loci associated with eruption of permanent teeth

    DEFF Research Database (Denmark)

    Geller, Frank; Feenstra, Bjarke; Zhang, Hao

    2011-01-01

    The sequence and timing of permanent tooth eruption is thought to be highly heritable and can have important implications for the risk of malocclusion, crowding, and periodontal disease. We conducted a genome-wide association study of number of permanent teeth erupted between age 6 and 14 years...

  16. A genome-wide association study identifies an osteoarthritis susceptibility locus on chromosome 7q22

    NARCIS (Netherlands)

    J.M. Kerkhof (Hanneke); R.J. Lories (Rik); I. Meulenbelt (Ingrid); I. Jonsdottir (Ingileif); A.M. Valdes (Ana Maria); P.P. Arp (Pascal); T. Ingvarsson (Torvaldur); M. Jhamai (Mila); H. Jonsson (Helgi); L. Stolk (Lisette); G. Thorleifsson (Gudmar); G. Zhai (Guangju); F. Zhang (Feng); Y. Zhu (Yicheng); R. van der Breggen (Ruud); M. Doherty (Michael); D. Felson; A. Gonzalez (Antonio); B.V. Halldorsson (Bjarni); D.J. Hart (Deborah); V.B. Hauksson (Valdimar); A. Hofman (Albert); J.P.A. Ioannidis (John); M. Kloppenburg (Margreet); N.E. Lane (Nancy); J. Loughlin (John); F.P. Luyten (Frank); M.C. Nevitt (Michael); N. Parimi (Neeta); H.A.P. Pols (Huib); F. Rivadeneira Ramirez (Fernando); E. Slagboom (Eline); U. Styrkarsdottir (Unnur); A. Tsezou (Aspasia); T. van de Putte (Tom); J. Zmuda (Joseph); T.D. Spector (Timothy); J-A. Zwart (John-Anker); A.G. Uitterlinden (André); J.B.J. van Meurs (Joyce); A.J. Carr (Andrew Jonathan)

    2010-01-01

    markdownabstract__Objective__ To identify novel genes involved in osteoarthritis (OA), by means of a genome-wide association study. Methods. We tested 500,510 single-nucleotide polymorphisms (SNPs) in 1,341 Dutch Caucasian OA cases and 3,496 Dutch Caucasian controls. SNPs associated with at least 2

  17. Genome-wide association study identifies 74 loci associated with educational attainment

    NARCIS (Netherlands)

    Okbay, Aysu; Beauchamp, Jonathan P.; Fontana, Mark Alan; Lee, James J.; Pers, Tune H.; Rietveld, Cornelius A.; Turley, Patrick; Chen, Guo-Bo; Emilsson, Valur; Meddens, S. Fleur W.; Oskarsson, Sven; Pickrell, Joseph K.; Thom, Kevin; Timshel, Pascal; de Vlaming, Ronald; Abdellaoui, Abdel; Ahluwalia, Tarunveer S.; Bacelis, Jonas; Baumbach, Clemens; Bjornsdottir, Gyda; Brandsma, Johannes H.; Concas, Maria Pina; Derringer, Jaime; Furlotte, Nicholas A.; Galesloot, Tessel E.; Girotto, Giorgia; Gupta, Richa; Hall, Leanne M.; Harris, Sarah E.; Hofer, Edith; Horikoshi, Momoko; Huffman, Jennifer E.; Kaasik, Kadri; Kalafati, Ioanna P.; Karlsson, Robert; Kong, Augustine; Lahti, Jari; van der Lee, Sven J.; de Leeuw, Christiaan; Lind, Penelope A.; Lindgren, Karl-Oskar; Liu, Tian; Mangino, Massimo; Marten, Jonathan; Mihailov, Evelin; Miller, Michael B.; van der Most, Peter J.; Oldmeadow, Christopher; Payton, Antony; Pervjakova, Natalia; Peyrot, Wouter J.; Qian, Yong; Raitakari, Olli; Rueedi, Rico; Salvi, Erika; Schmidt, Brge; Schraut, Katharina E.; Shi, Jianxin; Smith, Albert V.; Poot, Raymond A.; St Pourcain, Beate; Teumer, Alexander; Thorleifsson, Gudmar; Verweij, Niek; Vuckovic, Dragana; Wellmann, Juergen; Westra, Harm-Jan; Yang, Jingyun; Zhao, Wei; Zhu, Zhihong; Alizadeh, Behrooz Z.; Amin, Najaf; Bakshi, Andrew; Baumeister, Sebastian E.; Biino, Ginevra; Bonnelykke, Klaus; Boyle, Patricia A.; Campbell, Harry; Cappuccio, Francesco P.; Davies, Gail; De Neve, Jan-Emmanuel; Deloukas, Panos; Demuth, Ilja; Ding, Jun; Eibich, Peter; Eisele, Lewin; Eklund, Niina; Evans, David M.; Faul, Jessica D.; Feitosa, Mary F.; Forstner, Andreas J.; Gandin, Ilaria; Gunnarsson, Bjarni; Halldorsson, Bjarni V.; Harris, Tamara B.; Heath, Andrew C.; Hocking, Lynne J.; Holliday, Elizabeth G.; Homuth, Georg; Horan, Michael A.; Hottenga, Jouke-Jan; de Jager, Philip L.; Joshi, Peter K.; Jugessur, Astanand; Kaakinen, Marika A.; Kahonen, Mika; Kanoni, Stavroula; Keltigangas-Jarvinen, Liisa; Kiemeney, Lambertus A. L. M.; Kolcic, Ivana; Koskinen, Seppo; Kraja, Aldi T.; Kroh, Martin; Kutalik, Zoltan; Latvala, Antti; Launer, Lenore J.; Lebreton, Mael P.; Levinson, Douglas F.; Lichtenstein, Paul; Lichtner, Peter; Liewald, David C. M.; Loukola, Anu; Madden, Pamela A.; Magi, Reedik; Maki-Opas, Tomi; Marioni, Riccardo E.; Marques-Vidal, Pedro; Meddens, Gerardus A.; McMahon, George; Meisinger, Christa; Meitinger, Thomas; Milaneschi, Yusplitri; Milani, Lili; Montgomery, Grant W.; Myhre, Ronny; Nelson, Christopher P.; Nyholt, Dale R.; Ollier, William E. R.; Palotie, Aarno; Paternoster, Lavinia; Pedersen, Nancy L.; Petrovic, Katja E.; Porteous, David J.; Raikkonen, Katri; Ring, Susan M.; Robino, Antonietta; Rostapshova, Olga; Rudan, Igor; Rustichini, Aldo; Salomaa, Veikko; Sanders, Alan R.; Sarin, Antti-Pekka; Schmidt, Helena; Scott, Rodney J.; Smith, Blair H.; Smith, Jennifer A.; Staessen, Jan A.; Steinhagen-Thiessen, Elisabeth; Strauch, Konstantin; Terracciano, Antonio; Tobin, Martin D.; Ulivi, Sheila; Vaccargiu, Simona; Quaye, Lydia; van Rooij, Frank J. A.; Venturini, Cristina; Vinkhuyzen, Anna A. E.; Volker, Uwe; Volzke, Henry; Vonk, Judith M.; Waage, Johannes; Ware, Erin B.; Willemsen, Gonneke; Attia, John R.; Bennett, David A.; Berger, Klaus; Bertram, Lars; Bisgaard, Hans; Boomsma, Dorret I.; Borecki, Ingrid B.; Bultmann, Ute; Chabris, Christopher F.; Cucca, Francesco; Cusi, Daniele; Deary, Ian J.; Dedoussis, George V.; van Duijn, Cornelia M.; Eriksson, Johan G.; Franke, Barbara; Franke, Lude; Gasparini, Paolo; Gejman, Pablo V.; Gieger, Christian; Grabe, Hans-Jorgen; Gratten, Jacob; Groenen, Patrick J. F.; Gudnason, Vilmundur; van der Harst, Pim; Hayward, Caroline; Hinds, David A.; Hoffmann, Wolfgang; Hyppnen, Elina; Iacono, William G.; Jacobsson, Bo; Jarvelin, Marjo-Riitta; Jockel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L. R.; Lehtimaki, Terho; Lehrer, Steven F.; Magnusson, Patrik K. E.; Martin, Nicholas G.; McGue, Matt; Metspalu, Andres; Pendleton, Neil; Penninx, Brenda W. J. H.; Perola, Markus; Pirastu, Nicola; Pirastu, Mario; Polasek, Ozren; Posthuma, Danielle; Power, Christine; Province, Michael A.; Samani, Nilesh J.; Schlessinger, David; Schmidt, Reinhold; Sorensen, Thorkild I. A.; Spector, Tim D.; Stefansson, Kari; Thorsteinsdottir, Unnur; Thurik, A. Roy; Timpson, Nicholas J.; Tiemeier, Henning; Tung, Joyce Y.; Uitterlinden, Andre G.; Vitart, Veronique; Vollenweider, Peter; Weir, David R.; Wilson, James F.; Wright, Alan F.; Conley, Dalton C.; Krueger, Robert F.; Smith, George Davey; Hofman, Albert; Laibson, David I.; Medland, Sarah E.

    2016-01-01

    Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals(1). Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends

  18. Genome-wide association study identifies 74 loci associated with educational attainment

    NARCIS (Netherlands)

    A. Okbay (Aysu); J.P. Beauchamp (Jonathan); Fontana, M.A. (Mark Alan); J.J. Lee (James J.); T.H. Pers (Tune); Rietveld, C.A. (Cornelius A.); P. Turley (Patrick); Chen, G.-B. (Guo-Bo); V. Emilsson (Valur); Meddens, S.F.W. (S. Fleur W.); Oskarsson, S. (Sven); Pickrell, J.K. (Joseph K.); Thom, K. (Kevin); Timshel, P. (Pascal); R. de Vlaming (Ronald); M. Abdellaoui (Mohammed); T.S. Ahluwalia (Tarunveer Singh); J. Bacelis (Jonas); C. Baumbach (Clemens); Bjornsdottir, G. (Gyda); J.H. Brandsma (Johan); Pina Concas, M. (Maria); J. Derringer; Furlotte, N.A. (Nicholas A.); T.E. Galesloot (Tessel); S. Girotto; Gupta, R. (Richa); L.M. Hall (Leanne M.); S.E. Harris (Sarah); E. Hofer; Horikoshi, M. (Momoko); J.E. Huffman (Jennifer E.); Kaasik, K. (Kadri); I.-P. Kalafati (Ioanna-Panagiota); R. Karlsson (Robert); A. Kong (Augustine); J. Lahti (Jari); S. van der Lee (Sven); Deleeuw, C. (Christiaan); P.A. Lind (Penelope); Lindgren, K.-O. (Karl-Oskar); Liu, T. (Tian); M. Mangino (Massimo); J. Marten (Jonathan); E. Mihailov (Evelin); M. Miller (Mike); P.J. van der Most (Peter); C. Oldmeadow (Christopher); A. Payton (Antony); N. Pervjakova (Natalia); W.J. Peyrot (Wouter ); Qian, Y. (Yong); O. Raitakari (Olli); Rueedi, R. (Rico); Salvi, E. (Erika); Schmidt, B. (Börge); Schraut, K.E. (Katharina E.); Shi, J. (Jianxin); A.V. Smith (Albert Vernon); R.A. Poot (Raymond); B. St Pourcain (Beate); A. Teumer (Alexander); G. Thorleifsson (Gudmar); N. Verweij (Niek); D. Vuckovic (Dragana); Wellmann, J. (Juergen); H.J. Westra (Harm-Jan); Yang, J. (Jingyun); Zhao, W. (Wei); Zhu, Z. (Zhihong); B.Z. Alizadeh (Behrooz); N. Amin (Najaf); Bakshi, A. (Andrew); S.E. Baumeister (Sebastian); G. Biino; K. Bønnelykke (Klaus); P.A. Boyle (Patricia); H. Campbell (Harry); Cappuccio, F.P. (Francesco P.); G. Davies (Gail); J.E. de Neve (Jan-Emmanuel); P. Deloukas (Panagiotis); I. Demuth (Ilja); Ding, J. (Jun); Eibich, P. (Peter); Eisele, L. (Lewin); N. Eklund (Niina); D.M. Evans (David); J.D. Faul (Jessica D.); M.F. Feitosa (Mary Furlan); A.J. Forstner; I. Gandin (Ilaria); Gunnarsson, B. (Bjarni); B.V. Halldorsson (Bjarni); T.B. Harris (Tamara); E.G. Holliday (Elizabeth); A.C. Heath (Andrew C.); L.J. Hocking; G. Homuth (Georg); M. Horan (Mike); J.J. Hottenga (Jouke Jan); P.L. de Jager (Philip); P.K. Joshi (Peter); A. Juqessur (Astanand); M. Kaakinen (Marika); M. Kähönen (Mika); S. Kanoni (Stavroula); Keltigangas-Järvinen, L. (Liisa); L.A.L.M. Kiemeney (Bart); I. Kolcic (Ivana); Koskinen, S. (Seppo); A. Kraja (Aldi); Kroh, M. (Martin); Z. Kutalik (Zoltán); A. Latvala (Antti); L.J. Launer (Lenore); Lebreton, M.P. (Maël P.); D.F. Levinson (Douglas F.); P. Lichtenstein (Paul); P. Lichtner (Peter); D.C. Liewald (David C.); A. Loukola (Anu); P.A. Madden (Pamela); R. Mägi (Reedik); Mäki-Opas, T. (Tomi); R.E. Marioni (Riccardo); P. Marques-Vidal; Meddens, G.A. (Gerardus A.); G. Mcmahon (George); C. Meisinger (Christa); T. Meitinger (Thomas); Milaneschi, Y. (Yusplitri); L. Milani (Lili); G.W. Montgomery (Grant); R. Myhre (Ronny); C.P. Nelson (Christopher P.); D.R. Nyholt (Dale); W.E.R. Ollier (William); A. Palotie (Aarno); L. Paternoster (Lavinia); N.L. Pedersen (Nancy); K. Petrovic (Katja); D.J. Porteous (David J.); K. Räikkönen (Katri); Ring, S.M. (Susan M.); A. Robino (Antonietta); O. Rostapshova (Olga); I. Rudan (Igor); A. Rustichini (Aldo); V. Salomaa (Veikko); Sanders, A.R. (Alan R.); A.-P. Sarin; R. Schmidt (Reinhold); R.J. Scott (Rodney); B.H. Smith (Blair); J.A. Smith (Jennifer A); J.A. Staessen (Jan); E. Steinhagen-Thiessen (Elisabeth); K. Strauch (Konstantin); A. Terracciano; M.D. Tobin (Martin); S. Ulivi (Shelia); S. Vaccargiu (Simona); L. Quaye (Lydia); F.J.A. van Rooij (Frank); C. Venturini (Cristina); A.A.E. Vinkhuyzen (Anna A.); U. Völker (Uwe); Völzke, H. (Henry); J.M. Vonk (Judith); D. Vozzi (Diego); J. Waage (Johannes); E.B. Ware (Erin B.); G.A.H.M. Willemsen (Gonneke); J. Attia (John); D.A. Bennett (David A.); Berger, K. (Klaus); L. Bertram (Lars); H. Bisgaard (Hans); D.I. Boomsma (Dorret); I.B. Borecki (Ingrid); U. Bültmann (Ute); C.F. Chabris (Christopher F.); F. Cucca (Francesco); D. Cusi (Daniele); I.J. Deary (Ian J.); G.V. Dedoussis (George); C.M. van Duijn (Cock); K. Hagen (Knut); B. Franke (Barbara); L. Franke (Lude); P. Gasparini (Paolo); P.V. Gejman (Pablo); C. Gieger (Christian); H.J. Grabe (Hans Jörgen); J. Gratten (Jacob); P.J.F. Groenen (Patrick); V. Gudnason (Vilmundur); P. van der Harst (Pim); C. Hayward (Caroline)

    2016-01-01

    textabstractEducational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that

  19. A mega-analysis of genome-wide association studies for major depressive disorder

    NARCIS (Netherlands)

    Sullivan, Patrick F.; Daly, Mark J.; Ripke, Stephan; Lewis, Cathryn M.; Lin, Dan-Yu; Wray, Naomi R.; Neale, Benjamin; Levinson, Douglas F.; Breen, Gerome; Byrne, Enda M.; Wray, Naomi R.; Levinson, Douglas F.; Rietschel, Marcella; Hoogendijk, Witte; Ripke, Stephan; Sullivan, Patrick F.; Hamilton, Steven P.; Levinson, Douglas F.; Lewis, Cathryn M.; Ripke, Stephan; Weissman, Myrna M.; Wray, Naomi R.; Breuer, Rene; Cichon, Sven; Degenhardt, Franziska; Frank, Josef; Gross, Magdalena; Herms, Stefan; Hoefels, Susanne; Maier, Wolfgang; Mattheisen, Manuel; Noeethen, Markus M.; Rietschel, Marcella; Schulze, Thomas G.; Steffens, Michael; Treutlein, Jens; Boomsma, Dorret I.; De Geus, Eco J.; Hoogendijk, Witte; Hottenga, Jouke Jan; Jung-Ying, Tzeng; Lin, Dan-Yu; Middeldorp, Christel M.; Nolen, Willem A.; Penninx, Brenda P.; Smit, Johannes H.; Sullivan, Patrick F.; van Grootheest, Gerard; Willemsen, Gonneke; Zitman, Frans G.; Coryell, William H.; Knowles, James A.; Lawson, William B.; Levinson, Douglas F.; Potash, James B.; Scheftner, William A.; Shi, Jianxin; Weissman, Myrna M.; Holsboer, Florian; Muglia, Pierandrea; Tozzi, Federica; Blackwood, Douglas H. R.; Boomsma, Dorret I.; De Geus, Eco J.; Hottenga, Jouke Jan; MacIntyre, Donald J.; McIntosh, Andrew; McLean, Alan; Middeldorp, Christel M.; Penninx, Brenda P.; Ripke, Stephan; Smit, Johannes H.; Sullivan, Patrick F.; van Grootheest, Gerard; Willemsen, Gonneke; Zitman, Frans G.; van den Oord, Edwin J. C. G.; Holsboer, Florian; Lucae, Susanne; Binder, Elisabeth; Mueller-Myhsok, Bertram; Ripke, Stephan; Czamara, Darina; Kohli, Martin A.; Ising, Marcus; Uhr, Manfred; Bettecken, Thomas; Barnes, Michael R.; Breen, Gerome; Craig, Ian W.; Farmer, Anne E.; Lewis, Cathryn M.; McGuffin, Peter; Muglia, Pierandrea; Byrne, Enda; Gordon, Scott D.; Heath, Andrew C.; Henders, Anjali K.; Hickie, Ian B.; Madden, Pamela A. F.; Martin, Nicholas G.; Montgomery, Grant M.; Nyholt, Dale R.; Pergadia, Michele L.; Wray, Naomi R.; Hamilton, Steven P.; McGrath, Patrick J.; Shyn, Stanley I.; Slager, Susan L.; Oskarsson, Hoegni; Sigurdsson, Engilbert; Stefansson, Hreinn; Stefansson, Kari; Steinberg, Stacy; Thorgeirsson, Thorgeir; Levinson, Douglas F.; Potash, James B.; Shi, Jianxin; Weissman, Myrna M.; Guipponi, Michel; Lewis, Glyn; O'Donovan, Michael; Tansey, Katherine E.; Uher, Rudolf; Coryell, William H.; Knowles, James A.; Lawson, William B.; Levinson, Douglas F.; Potash, James B.; Scheftner, William A.; Shi, Jianxin; Weissman, Myrna M.; Castro, Victor M.; Churchill, Susanne E.; Fava, Maurizio; Gainer, Vivian S.; Gallagher, Patience J.; Goryachev, Sergey; Iosifescu, Dan V.; Kohane, Isaac S.; Murphy, Shawn N.; Perlis, Roy H.; Smoller, Jordan W.; Weilburg, Jeffrey B.; Kutalik, Zoltan; Preisig, Martin; Grabe, Hans J.; Nauck, Matthias; Schulz, Andrea; Teumer, Alexander; Voelzke, Henry; Landen, Mikael; Lichtenstein, Paul; Magnusson, Patrik; Pedersen, Nancy; Viktorin, Alexander

    2013-01-01

    Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chro

  20. A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium

    NARCIS (Netherlands)

    McKay, J.D.; Truong, T.; Gaborieau, V.; Chabrier, A.; Chuang, S.C.; Byrnes, G.; Zaridze, D.; Shangina, O.; Szeszenia-Dabrowska, N.; Lissowska, J.; Rudnai, P.; Fabianova, E.; Bucur, A.; Bencko, V.; Holcatova, I.; Janout, V.; Foretova, L.; Lagiou, P.; Trichopoulos, D.; Benhamou, S.; Bouchardy, C.; Ahrens, W.; Merletti, F.; Richiardi, L.; Talamini, R.; Barzan, L.; Kjaerheim, K.; Macfarlane, G.J.; Macfarlane, T.V.; Simonato, L.; Canova, C.; Agudo, A.; Castellsague, X.; Lowry, R.; Conway, D.I.; McKinney, P.A.; Healy, C.M.; Toner, M.E.; Znaor, A.; Curado, M.P.; Koifman, S.; Menezes, A.; Wunsch-Filho, V.; Neto, J.E.; Garrote, L.F.; Boccia, S.; Cadoni, G.; Arzani, D.; Olshan, A.F.; Weissler, M.C.; Funkhouser, W.K.; Luo, J.; Lubinski, J.; Trubicka, J.; Lener, M.; Oszutowska, D.; Schwartz, S.M.; Chen, C.; Fish, S.; Doody, D.R.; Muscat, J.E.; Lazarus, P.; Gallagher, C.J.; Chang, S.C.; Zhang, Z.F.; Wei, Q.; Sturgis, E.M.; Wang, L.E.; Franceschi, S.; Herrero, R.; Kelsey, K.T.; McClean, M.D.; Marsit, C.J.; Nelson, H.H.; Romkes, M.; Buch, S.; Nukui, T.; Zhong, S.; Lacko, M.; Manni, J.J.; Peters, W.H.M.; Hung, R.J.; McLaughlin, J.; Vatten, L.; Njolstad, I.; Goodman, G.E.; Field, J.K.; Liloglou, T.; Vineis, P.; Clavel-Chapelon, F.; Palli, D.; Tumino, R.; Krogh, V.; Panico, S.; Gonzalez, C.A.; Quiros, J.R.; Martinez, C.; Navarro, C.; Ardanaz, E.; Larranaga, N.

    2011-01-01

    Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers.

  1. A genome wide association study links glutamate receptor pathway to sporadic Creutzfeldt-Jakob disease risk

    NARCIS (Netherlands)

    P. Sanchez-Juan (Pascual); M.T. Bishop (Matthew); G.G. Kovacs (Gabor); M. Calero (Miguel); Y.S. Aulchenko (Yurii); A. Ladogana (Anna); A. Boyd (Alison); V. Lewis (Victoria); C. Ponto (Claudia); Calero, O. (Olga); A. Poleggi (Anna); A. Carracedo (Angel); S. van der Lee (Sven); T. Ströbel (Thomas); F. Rivadeneira Ramirez (Fernando); A. Hofman (Albert); S. Haik; O. Combarros (Onofre); J. Berciano (José); A.G. Uitterlinden (André); S.J. Collins (Steven); H. Budka (Herbert); J-P. Brandel (Jean-Philippe); J.-L. Laplanche (Jean-Louis); M. Pocchiari (Maurizio); I. Zerr (Inga); R. Knight (Richard); R.G. Will (Robert); C.M. van Duijn (Cock)

    2015-01-01

    textabstractWe performed a genome-wide association (GWA) study in 434 sporadic Creutzfeldt-Jakob disease (sCJD) patients and 1939 controls from the United Kin